Dr. Wakefield Sues Brian Deer and BMJ's Fiona Godlee
That’s My Boy!

The Inflammation Highway: aka Autism

  Tummy-ache-abdominal-pain-t13513By Lisa Goes

"The one thing about my husband and I...we laugh...A lot. We find a way. We really do. Poop filled sleepless nights, injuries, missed appointments, clutter everywhere, missing paperwork...sometimes all you can do is laugh. But today, looking at the dark circles we've seen so many times under our children's eyes, seeing the suffering, the real genuine human suffering that we have worked for three years to alleviate...to see it reach these depths...there is no laughing today. There is sadness. Even the fight is gone. I should be sleeping, but I have to read up on one of our new remedies. Maybe this will be the one that touches his immune damage and regulates him? Maybe. Maybe, it will work for him like it has for THOUSANDS of other children. Maybe. I can't sleep when this could be it and I could be calling the next doctor tomorrow and we could have one less day of this. Plus, I already have an appointment to see a doctor tomorrow and I will need him to know that I know what I'm talking about. If there is one thing you learn as an autism parent it is that YOU MUST KNOW WHAT YOU ARE TALKING ABOUT WITH DOCTORS. You must learn to speak their language. If you don't you will get dismissed. Must read, now.

But, before I go, just need to let everyone know the women who work for us are angels from God. They were hurt today. Two of them. In their sweetest voices they kept repeating, "nice hands." And "time to get down monkey" when he climbed on the counter for the 27th time on their shift. He is 50 lbs now. Very fast and very strong. They get him. They see the real Noah in there, fighting like hell. He is mad. In fact, that's what he said in therapy today, "I'm MAD!" His therapists were thrilled. They were so excited to see him emote appropriately. I agree with them, it's encouraging. It's just that, he's mad he's sick. He's mad his head hurts all the time. He's mad his three year old brother can use the toliet and he cannot. He's mad that his body is rebelling against him and everything hurts. He's mad that in addition to not getting to go where everyone else goes and doing all the fun things other 5 year olds do, he also cannot EAT anything they do. It seems cruel doesn't it? It is.

Autism is the cruelest most malicious, devious, conniving, heinous disease. If you fear the chicken pox or diarrhea more you are in big, big trouble. Because I guarantee with the new schedule autism will come a knocking at your door. And it will get in. It finds a way. Sometimes it looks like OCD, sometimes it looks like ADHD, even arthritis. "That's nuts!", you say. Not really. It should all just be called autism. Because any time pharma causes inflammation they don't want you to find out about, they just make up a word for it. Autism. Asthma. ADD. Just made up words for inflammation. Off to read ABOUT AUTISM . It's a good one, you might want to check it out yourself... Much hope for all our beautiful children. xo lj "

Lisa Goes is Contributing Editor to Age of Autism.



Forgot the link to add the last abstract.

Analysis of neurodevelopmental delay in children exposed in utero to hyperemesis gravidarum reveals increased reporting of autism spectrum disorder



Like to read the whole report, though have already surmised this. Search back this thread if interested.

Analysis of neurodevelopmental delay in children exposed in utero to hyperemesis gravidarum reveals increased reporting of autism spectrum disorder


• Neurodevelopmental diagnoses in children exposed to Hyperemesis Gravidarum were compared to diagnoses in unexposed children.
• Hyperemesis Gravidarum may be associated with a 3-fold increase in odds of having a neurodevelopmental diagnosis ∼age 12.
• 8% (22/267) of children exposed to HG in utero were reported by mothers to have an autism spectrum disorder (ASD) diagnosis.
• None (0/93) of the unexposed children were reported by their mothers to have ASD.
• As early intervention for ASD can be critical to prognosis, larger studies are urgently needed to confirm the findings.


"The purpose of this study was to follow up on the reporting of neurodevelopmental disorders in children exposed in utero to Hyperemesis Gravidarum (HG). This was an exploratory descriptive study whereby neurodevelopmental outcomes of 267 children delivered by 177 mothers with HG were compared to neurodevelopmental outcomes from 93 children delivered by 60 unaffected mothers. Similar to at age 8, the children (now 12) exposed in utero to HG had over 3-fold increase in odds of neurodevelopmental disorders including attention, anxiety, sensory, sleep difficulty, and social development delay/social anxiety. However, with the longer follow-up, there was also a significant increase in Autism Spectrum Disorder (ASD), reported in 22/267 (8%) of children exposed to HG in utero and no unexposed children. As early intervention for ASD can be critical to prognosis, larger studies are urgently needed to determine whether ASD is associated with exposure to HG."


Some Science of the Soul {from a sinner}



interesting visitor.
Dr Horowitz had a slide about chemokine signature for borreliosis infections about 17:30 in this lecture at lymeMIND


An additional part from the Wiki entry on CCR4 I quoted a bit from about chemokines involved mentioned in the last post I should have added this. Sometimes I assume people are seeing the things I find naturally involved. This pertains to the angiogenesis I have been highlighting in this thread as it relates to CCR4/CCL17. I will just repost what I did before plus the last paragraph added.

"The protein encoded by this gene belongs to the G protein-coupled receptor family. It is a receptor for the following CC chemokines:

CCL2 (MCP-1)
CCL4 (MIP-1)
CCL17 (TARC)[8]
CCL22 (Macrophage-derived chemokine)[9]

"Chemokines are a group of small structurally related proteins that regulate cell trafficking of various types of leukocytes. The chemokines also play fundamental roles in the development, homeostasis, and function of the immune system, and they have effects on cells of the central nervous system as well as on endothelial cells involved in angiogenesis or angiostasis.[7] "



The irresistible CCL17

New role for the allergy driver: It influences signal transmission in the brain

"The chemotactic protein CCL17 attracts immune cells to where they are currently needed. Doctors have long known: A high level of this substance in the body indicates an allergic reaction. A team of scientists led by the University of Bonn has now discovered a completely new function: CCL17 also influences signal transmission in the brain. There may even be a molecular link to autism. The results have now been published in the journal Glia.

Chemotactic cytokines, chemokines for short, are signaling proteins that act like an attractant and ensure, for example, that immune cells migrate from the bloodstream into the tissues. The chemokine CCL17 is known to increase inflammation and is associated with allergic diseases. A high level of CCL17 in the blood is regarded by doctors as a diagnostic marker of ongoing allergic reactions such as atopic eczema. The further the research on chemokines progresses, however, the more functions are discovered. Thus, an earlier joint study by the Universities of Münster and Bonn showed that animals with a defect in the expression of the receptor for CCL17 have behavioral problems: For example, they were unable to build proper nests like their normally developed mates.

"These behavioral changes indicated that CCL17 not only affects the immune system but perhaps also the brain," explains the corresponding author of the study, Prof. Dr. Irmgard Förster from the LIMES Institute at the University of Bonn, who is also a member of the Cluster of Excellence "ImmunoSensation." If there is such a connection, which cells in the brain produce CCL17? This question was investigated by doctoral student Lorenz Fülle and Irmgard Förster, together with scientists from the Institute of Cellular Neurosciences around Prof. Dr. Christian Henneberger, Dr. Annett Halle from the German Center for Neurodegenerative Diseases (DZNE) and Dr. Judith Alferink from the University of Münster.

Through a genetic modification, the researchers coupled the release of CCL17 with the production of a fluorescent dye that illuminated all cells that produce the chemokine. The scientists additionally stimulated CCL17 production by simulating an infection using a substance contained in bacterial cell membranes. The production sites of the chemokine in the brain were then clearly visible under the microscope. "CCL17 is mainly produced by neurons of the hippocampus," reports lead author Lorenz Fülle. This structure, which is shaped like a seahorse, is present on the right and left side of the brain, and fulfills an important function in tasks such as orientation and memory formation.

Scientists blocked the gene for CCL17

As a next step, the scientists blocked the gene for CCL17 production and observed the effect. In the absence of the chemokine, the microglial cells in these "knockout" mice were significantly smaller and there were only half as many as in untreated control animals. Microglial cells have long been known as immune cells of the brain, where they take responsibility as "health guards" for the disposal of cell debris and infectious agents. Meanwhile, it has been shown that these "scavenger cells" also directly support the work of the neurons independently of their phagocytic activity.

In order to investigate the effect of CCL17 on the function of neurons, scientists in the laboratory of Prof. Dr. Christian Henneberger at the Institute of Cellular Neurosciences (University of Bonn Medical School) examined neuronal signaling in the brain. Henneberger: "The experiments indicate that CCL17 attenuates signal transmission in the hippocampal region of the brain." Since autism in humans is also associated with elevated levels of CCL17 in the blood, CCL17 could also play a role in this developmental disorder, for example due to an infection or an allergic reaction in early childhood. "But so far these are speculations," says Förster. "The exact effects of CCL17 have yet to be demonstrated by further research."


The C-C Chemokines CCL17 and CCL22 and Their Receptor CCR4 in CNS Autoimmunity.

"The C-C class chemokines 17 (CCL17) and 22 (CCL22) and their C-C chemokine receptor 4 (CCR4) have been shown to play an important role in homeostasis and inflammatory responses. Here, we provide an overview of the involvement of CCR4 and its ligands in CNS autoimmunity."

Here is some info from a report I posted here in 2013.

Elevated serum levels of macrophage-derived chemokine and thymus and activation-regulated chemokine in autistic children


In some autistic children, there is an imbalance of T helper (Th)1/Th2 lymphocytes toward Th2, which may be responsible for the induction of the production of autoantibodies in these children. Th2 lymphocytes express CCR4 receptors. CCR4 ligands include macrophage-derived chemokine (MDC) and thymus and activation-regulated chemokine (TARC). They direct trafficking and recruitment of Th2 cells. We are the first to measure serum levels of CCR4 ligands in relation to the degree of the severity of autism...


Serum levels of CCR4 ligands were elevated in autistic children and they were significantly correlated to the degree of the severity of autism. However, further research is warranted to determine the pathogenic role of CCR4 ligands in autism and to shed light on the therapeutic role of CCR4-ligand antagonism in autistic children."


CCR4 -Wiki

The protein encoded by this gene belongs to the G protein-coupled receptor family. It is a receptor for the following CC chemokines:
CCL2 (MCP-1)
CCL4 (MIP-1)
CCL17 (TARC)[8]
CCL22 (Macrophage-derived chemokine)[9]


John Stone


This is probably a technical problem to do with the updating of the platform (which has been going on an annoyingly long time).


Regarding the last [post, it also brings up "This site is not secure. If you simply copy the link address and paste it in to a browser address bar it will bring up the report. It seems to not be willing to link from this host.


I posted a link to a report in the last post. Upon clicking on it now it says "This site is nor secure" and shows no report.

Here is the updated link to that report.

p38α MAPK signaling drives pharmacologically reversible brain and gastrointestinal phenotypes in the SERT Ala56 mouse



Don't know where to start, but here is a thing I had been into a few years back on this thread about
p38α MAPK. This is mitochondrially related.

Scientists pinpoint pathway that impacts features of autism

the report on this release

p38α MAPK signaling drives pharmacologically reversible brain and gastrointestinal phenotypes in the SERT Ala56 mouse



Autophagy in inflammation: the p38α MAPK-ULK1 axis


p38 MAPK inhibits autophagy and promotes microglial inflammatory responses by phosphorylating ULK1.



So many songs filled with wisdom. They rarely provide answers, but they are genius in asking sustaining questions. AoA is a defining pulse.


Having posted elsewhere on the sight on my view that the mother's microbiome and related immune(esp il-17} and system response influence Autism generation/risk and the pre natal health of the child, I though this piece gives some light. This is one particularly notable quote below.

TH17 cells in human recurrent pregnancy loss and pre-eclampsia

Systemic and local priming of TH17 cell differentiation in pregnancy
"Several differentiation factors and transcription factors that are unique to TH17 cells have been identified, marking TH17 cells as an independent subset of T helper cells. TGF-beta and IL-6 have been reported as the minimal requirements in mice for TH17 cell differentiation from naive CD4+ T cells; in contrast, IL-1beta plus IL-6 or IL-23 are required in human TH17 cells.47,48,49,50,51,52 IL-23/IL-23R plays an important role in stabilizing and endowing TH17 cells with pathogenic effector functions, that are regulated by serum glucocorticoid kinase 1.53 Compared with other TH lineages, including TH1, TH2 and Treg cells, TH17 cells have unique genetic programs to express the transcription factor RORgt, which induces the transcription of the Il17A gene.8 Other transcription factors, such as STAT3,54 RORalpha55 and interferon regulatory factor 4,56 have been reported to be important in TH17 differentiation. Aryl hydrocarbon receptor, an environmental toxin sensor, has also been identified as a regulator of TH17 cytokines, especially IL-22 production.57,58

In pregnancy, the fetus is similar to an allograft from the perspective of the maternal immune system. Trophoblast invasion from the allogeneic fetus and the shedding of fetal antigens may stimulate a maternal systemic inflammatory response and may therefore cause the emergence of TH17 cells. Contrary to Wegmann's hypothesis, it is surprising that many of the characteristics of a systemic inflammatory response have been demonstrated in normal pregnant women,59 including increased leukocytes,60 monocytic61 and phagocytic activity62 and the production of pro-inflammatory cytokines, such as IL-6, IL-12, IL-18 and TNF-alpha.63,64 A classical marker of inflammatory activity, C-reactive protein, is increased beginning as early as the fourth week of gestation.65 These phenomena show that pregnancy is a well-controlled systemic inflammatory state. Furthermore, it has been reported that subcellular microparticles that are shed from the placenta are present during normal pregnancy and are increased significantly in PE.66,67 These subcellular microparticles shed from the placenta are pro-inflammatory and can stimulate peripheral blood mononuclear cells in healthy non-pregnant females to produce TNF-alpha, IL-12, IL-18 and IFNG. Therefore, such microparticles might contribute to the maternal systemic inflammation observed in both normal and pre-eclamptic pregnancies.68 In addition, the microparticles, cellular debris and exosomes shed by the allogeneic fetus can be captured by antigen-presenting cells, contribute to the priming of fetal-reactive T cells during pregnancy.69 However, whether these fetal antigens have a direct relationship with the differentiation of TH17 has not yet been resolved.

We and others have observed low numbers of TH17 cells and low levels of the TH17-related mRNAs RORC and IL-23R in the deciduas during normal human pregnancy.25,70 In RSA, increased levels of inflammatory cytokines, including IL-6 and IL-1beta, have been observed, and these cytokines have a positive correlation with the proportion of TH17 cells.12,70 The inflammatory stimulus from local allogeneic fetal antigens, systematic inflammation and increased pro-inflammatory cytokines may induce the differentiation of TH17 cells during pregnancy."



I need to correct something. I said: "the receptor is in "every cell in the body".

The article actually says: "The genes for smell receptors are present in almost every cell of the body." It is this I find intriguing.


This article ties blood pressure to the microbiome effecting the kidneys. The substance propionate is identified as is acetate. I haven't fit this piece into the puzzle yet, but it is a part. The fact that the receptor is in "every cell in the body" makes it more intriguing. The whole piece is good.

How Bacteria Help Regulate Blood Pressure

"The researchers have uncovered a direct, molecular-level explanation of how the microbiome conspires with the kidneys and the blood vessels to manipulate the flow of blood.

The smell receptor, called Olfr78, was an orphan at first: It had previously been noticed in the sensory tissues of the nose, but no one knew what specific scent or chemical messenger it responded to. Pluznick began by testing various chemical possibilities and eventually narrowed down the candidates to acetate and propionate. These short-chain fatty acid molecules come from the fermentation breakdown of long chains of carbohydrates — what nutritionists call dietary fiber. Humans, mice, rats and other animals cannot digest fiber, but the bacteria that live in their guts can.

As a result, more than 99 percent of the acetate and propionate that floats through the bloodstream is released by bacteria as they feed. “Any host contribution is really minimal,” Pluznick said. Bacteria are therefore the only meaningful source of what activates Olfr78 — which, further experiments showed, is involved in the regulation of blood pressure.

Our bodies must maintain a delicate balance with blood pressure, as with electricity surging through a wire, where too much means an explosion and too little means a power outage. If blood pressure is too low, an organism loses consciousness; if it’s too high, the strain on the heart and blood vessels can be deadly. Because creatures are constantly flooding their blood with nutrients and chemical signals that alter the balance, the control must be dynamic. One of the ways the body exerts this control is with a hormone called renin, which makes blood vessels narrower when the pressure needs to be kept up. Olfr78, Pluznick and her colleagues discovered, helps drive the production of renin.

How did a smell receptor inherit this job? The genes for smell receptors are present in almost every cell of the body. If in the course of evolution these chemical sensors hooked up to the machinery for manufacturing a hormone rather than to a smell neuron, and if that connection proved useful, evolution would have preserved the arrangement, even in parts of the body as far from the nose as the kidneys are.

Olfr78 wasn’t the end of the story, however. While the team was performing these experiments, they realized that another receptor called Gpr41 was getting signals from the gut microbiome as well. In a paper last year, Pluznick’s first graduate student, Niranjana Natarajan, now a postdoctoral fellow at Harvard University, revealed the role of Gpr41, which she found on the inner walls of blood vessels. Like Olfr78, Gpr41 is known to respond to acetate and propionate — but it lowers blood pressure rather than raising it. Moreover, Gpr41 starts to respond at low levels of acetate and propionate, while Olfr78 kicks in only at higher levels.

Here’s how the pieces fit together: When you — or a mouse, or any other host organism whose organs and microbes talk this way — have a meal and dietary fiber hits the gut, bacteria feed and release their fatty-acid signal. This activates Gpr41, which ratchets down the blood pressure as all the consumed nutrients flood the circulation.

If you keep eating — a slice of pie at Thanksgiving dinner, another helping of mashed potatoes — Gpr41, left to itself, might bring the pressure down to dangerous levels. “We think that is where Olfr78 comes in,” Pluznick said. That receptor, triggered as the next surge of fatty acids arrives, keeps blood pressure from bottoming out by calling for renin to constrict the blood vessels.

The new understanding of how symbiotic bacteria manipulate blood pressure is emblematic of wider progress in linking the microbiome to our vital statistics and health. While vague statements about the microbiome’s effect on health have become commonplace in recent years, the field has moved beyond simply making associations, said Jack Gilbert, a microbiome researcher at the University of Chicago."



Getting warmer. How is it they so much when suddenly linking it to the mother's microbiome, {been there} like how vaccines could not have any influence. Please.Yet diet becomes a factor and antibiotics can cut both ways.

Autism risk determined by health of mom's gut

"While Lukens' work links the immune system with neurodevelopmental disorders, he emphasized that this in no way suggests that vaccines are contributing to the development of autism. "There's a definite link between the immune response and the developing brain," he said. "It just doesn't have anything to do with vaccines. It's much, much earlier.""


Just citing some of my past comments in this thread on the matter.

"It is worth considering that given that many vaccines require a healthy gut microbiome to work effectively, or at all, that the reason gut issues are occurring in some autism and other gut related problems is that it is the bodies attempt to prevent heightened immune response to vaccines, or dietary antigens, or simply a result of an already stimulated immune response, acquired from the mother, to disease pathogens reflecting a deregulated immune system or one hypersensitive."

Posted by: Visitor | January 09, 2016 at 05:32 PM


"It may be that vaccines are the main catalyst for the increase in many immune related conditions{fibro, CFS, and others}, but the cumulative vaccine effects are leading to a plethora of effected mothers who are now giving birth to children already headed into autism or more children more susceptible to vaccines themselves leading into autism. So, it is not that vaccines are not an issue in most cases, but that it is getting to where immune changes in mothers response to infection additional vaccines{flu shots} and conditioned immune status effecting infants prenatally too is more often than before enough to bring about autism even before an infant receives their vaccines.

If this is the case, it blurs the line in seeing where the insults take place and ignoring immune effects in mothers by vaccines misses the tie to increased autoimmune and inflammatory diseases in the population at large. Because of these effects a child can now be born with autism beyond the limited "gene only" causes."

Posted by: Visitor | January 09, 2016 at 05:00 PM


Genome-wide changes in protein translation efficiency are associated with autism

Supplementary Data





Sometimes those who post what you think arte off topic are trying to do a greater good then you have imagined, but thank you for your reply. I admire you, but I have approaches to help that may not be appreciated. I am those with autisms greatest supporters. The pure offensive approach without the intrinsic human appeal is lacking. I have been open including my confusion and pain. We as a community need to trust in this power of appeal to everyone as acknowledges others innate knowledge and desire for goodness to respond to the harm that is occurring. Our fellowman does care..

I realize I am not the best spokesman , but I was dismayed at how quickly AoA censored me when I am among their greatest advocates. Thank you for your response.

John Stone

Hi Visitor,

Sometimes we don’t post comments which seem off-topic.




With what I have contributed am I now banned?

Kate C

Dear Visitor, It's terrific to hear Rubenstein's Chopin in the morning. Thanks for that. It's amazing how music calls on different parts of the brain than logical thinking does. I'm wrestling with a Chopin nocturne these days. Sometimes it doesn't work at all, sometimes some of the pieces fall into place. Maybe I can get some of Rubenstein's emotional abandon eventually, but I seem to need to learn the notes before I can let go!




Trying to see things from what is needed for the genetic pool. A woman who could reflect and respond with this degree of biological dysfunction posses something that is of value to the genome. I was arrested by it, so I think I do as well. Exile for the remnant to add to the survival.

Since only Kate seems to get it I will just let the stream of consciousness go a bit and indulge myself since no one will ever believe me.


Hans Litten

Posted by: Visiitor | February 08, 2018 at 02:44 PM

Are you familiar with the website ?



Yes, I agree with Kate. I always learn good information from your posts, Visitor. But why such a heavy heart? It is not up to one person to save the world, or the tragically complex puzzle of autism. The outcome of this battle is not resting on your shoulders alone. And when you feel overwhelmed step back, pair down what you know to basics, step away from the screen, go out in the sun,put your feet on the ground, and take a deep breath. People are like rubber bands, we can stretch and stretch, but then we must contract for a while lest we snap. Once out from under the LEDs and fluorescents, find one person to help. They are in need are everywhere, and if you throw one small stone, you will make a ripple, whether you can see the other side of the pond where it might end or not. Go talk to the head of your nearest church, tell him or her how much you know about autism, explain the concept of biomedical solutions, and volunteer to start an exploration and support group for chronic illness. Post your meetings on the church bulletin board or in their weekly newsletter. Build it, they will come. Or maybe contemplate that God or the universe may be showing you that the person you need to help right now, for just a little while, is you. It is critical that people take time for themselves, and that's ok. Have you taken the time to apply the health principals we have all discussed on this site to yourself yet? You can't escape chemistry and physics yourself, you know? Your spirit cannot soar if it is mired in sludge.
How are your D3 levels? Are you eating low carb, higher fat? Have you switched your omega 6's to omega 3s? Are you getting the right and varied probiotics? Checked your B12/folate? Have you discovered topical magnesium? Rid yourself of toxic exposures? Turning off the wireless at night? Surrounding your workspace with sun-mimicking lightbulbs like halogens? Are you "minding your mito?" Grounding yourself while at the computer? Walking in nature periodically to appreciate the beauty that God gave us that still exists in the middle of the chaos. Nobody wants a smart person like you to push themselves to the point of self-sacrifice, that would be self-defeatist in the eyes of any autism-aware person.


Kate C,

I don't understand why I could not have become involved with someone like you, instead in what I was arrested by in my focus. That is a scientific statement, not a social one.


Kate C ,

To know that even one is so aware of these matters bolsters my spirit. I don't know if I can persist in searching for answers, but you give me hope. To infinity and beyond. Thank you for your kindness.


Kate C

Dear Visitor, I have always read and reread your posts. I value them because they are science-driven, compassionate approaches to finding the causes of autism. I hope that having gone "off the rails" refers to the period of time between your postings, and not to any feelings of inadequacy. Because from where I stand, you are incredibly competent and intelligent. Your postings give me hope. Please don't stop.


To anyone. I apologize that I have gone off the rails. I don't know if anything I have posted has ever made any difference, but I tried with every fiber my being to bring light to these matters. I have so much love and respect for almost all who post on AoA. I have found I am all too human and don't know if I am objective. The immensity of all this and my own personal experience makes discerning reality a fulltime challenge and more often I am thinking I cannot ever catchup. God bless Dr. Wakefield who has a character and insight that is pure blessing and defies description. I admire him from afar.

" Assembly-line medicine kills doctors. Brilliant, compassionate people can't care for complex patients in 15-minute slots. When punished or fired by administrators for "inefficiency" or "low productivity," doctors may become suicidal. Pressure from insurance companies and government mandates crush these talented people who just want to help patients. Many doctors cite inhumane working conditions in their suicide notes."


A lot of us have known about LPS, bacteria, and candida problems in autism forever, but trying to piece all the elements and processes into a complete picture from start to finish and understand the minute details of the processes makes for many recapitulations as though it is new, at least for me, when it is actually some stuff that was found and noted at the outset. I noticed a doctor's video on another thread about candida and there was a lot of truth in it. One of the first things we did was deal with the gut dysbiosis and candida. The constant dismissal over years made me think I had to continue to prove these aspects.

From many years back.
Gut Microorganisms and Autism: the Latest Research 1999 Sep 26-29


MIR-155 is a master inflammation regulator and as you say, is involved in many conditions. Ones that I have peaked my interest are H. Pylori control, arthritis, migraines, Diabetes, obesity, MS, Down syndrome, lupus, and of course autism. There is clearly a different amount of function in different conditions and the amounts in relation to foxp3, MIF, brain function and BBB integrity are on one side, but skin and gut function aspects of mir-155 seem to be out of sync, for lack of a better description at this point. Here are s a few info bits on it. Impaired signaling and development in T and B cells is a part of the issue it appears.

miR-155: an ancient regulator of the immune system


"MicroRNAs (miRNAs) are a newly recognized class of regulatory genes which repress the expression of protein-coding genes. Numerous studies have uncovered a complex role for miRNAs regulating many aspects of a variety of cellular processes including cell growth, differentiation, and lineage commitment. In the immune system, miR-155 is unique in its ability to shape the transcriptome of activated myeloid and lymphoid cells controlling diverse biological functions ranging from inflammation to immunological memory. Not surprisingly, a tight control of miR-155 expression is required to avoid malignant transformation, as evidenced by miR-155 overexpression in many cancers of B-cell origin. In this review, we discuss the potential of miR-155 as a molecular target for therapeutic intervention and discuss the function of miR-155 in the context of protective immunity. We first look back into the emergence of miR-155 in evolution, which is coincidental with the emergence of the ancestors of the antigen receptors. We then summarize what we have learned about the role of miR-155 in the regulation of lymphoid subsets at the cellular and molecular level in the context of recent progress in this field."


Requirement of bic/microRNA-155 for Normal Immune Function


"MicroRNAs are a class of small RNAs that are increasingly being recognized as important regulators of gene expression. Although hundreds of microRNAs are present in the mammalian genome, genetic studies addressing their physiological roles are at an early stage. We have shown that mice deficient for bic/microRNA-155 are immunodeficient and display increased lung airway remodeling. We demonstrate a requirement of bic/microRNA-155 for the function of B and T lymphocytes and dendritic cells. Transcriptome analysis of bic/microRNA-155–deficient CD4+ T cells identified a wide spectrum of microRNA-155–regulated genes, including cytokines, chemokines, and transcription factors. Our work suggests that bic/microRNA-155 plays a key role in the homeostasis and function of the immune system."


MicroRNA-155 is essential for the T cell-mediated control of Helicobacter pylori infection and for the induction of chronic Gastritis and Colitis.


"MicroRNAs govern immune responses to infectious agents, allergens, and autoantigens and function by posttranscriptional repression of their target genes. In this paper, we have addressed the role of microRNA-155 (miR-155) in the control of Helicobacter pylori infection of the gastrointestinal tract and the development of H. pylori-induced chronic gastritis and associated gastric preneoplastic pathology. We show that miR-155 is upregulated in the gastric mucosa of experimentally infected mice and that miR-155(-/-) mice fail to control H. pylori infection as a result of impaired pathogen-specific Th1 and Th17 responses. miR-155(-/-) mice are also less well protected against challenge infection after H. pylori-specific vaccination than their wild-type (wt) counterparts. As a consequence of their impaired T cell responses to H. pylori, miR-155(-/-) mice develop less severe infection-induced immunopathology manifesting as chronic atrophic gastritis, epithelial hyperplasia, and intestinal metaplasia. T cells from miR-155(-/-) mice that are activated by CD3/CD28 cross-linking expand less and produce less IFN-γ and IL-17 than wt T cells. Finally, we show in this paper using adoptive transfers that the phenotypes of miR-155(-/-) mice are likely due to T cell-intrinsic defects. In contrast to wt T cells, miR-155(-/-) T cells from infected donors do not control H. pylori infections in T cell-deficient recipients, do not differentiate into Th1 or Th17 cells, and do not cause immunopathology. In addition, naive miR-155(-/-) T cells fail to induce chronic Th17-driven colitis in an adoptive transfer model. In conclusion, miR-155 expression is required for the Th17/Th1 differentiation that underlies immunity to H. pylori infection on the one hand and infection-associated immunopathology on the other."


Helicobacter pylori Induces miR-155 in T Cells in a cAMP-Foxp3-Dependent Manner


"Amongst the most severe clinical outcomes of life-long infections with Helicobacter pylori is the development of peptic ulcers and gastric adenocarcinoma - diseases often associated with an increase of regulatory T cells. Understanding H. pylori-driven regulation of T cells is therefore of crucial clinical importance. Several studies have defined mammalian microRNAs as key regulators of the immune system and of carcinogenic processes. Hence, we aimed here to identify H. pylori-regulated miRNAs, mainly in human T cells. MicroRNA profiling of non-infected and infected human T cells revealed H. pylori infection triggers miR-155 expression in vitro and in vivo. By using single and double H. pylori mutants and the corresponding purified enzymes, the bacterial vacuolating toxin A (VacA) and γ-glutamyl transpeptidase (GGT) plus lipopolysaccharide (LPS) tested positive for their ability to regulate miR-155 and Foxp3 expression in human lymphocytes; the latter being considered as the master regulator and marker of regulatory T cells. RNAi-mediated knockdown (KD) of the Foxp3 transcription factor in T cells abolished miR-155 expression. Using adenylate cyclase inhibitors, the miR-155 induction cascade was shown to be dependent on the second messenger cyclic adenosine monophosphate (cAMP). Furthermore, we found that miR-155 directly targets the protein kinase A inhibitor α (PKIα) mRNA in its 3′UTR, indicative of a positive feedback mechanism on the cAMP pathway. Taken together, our study describes, in the context of an H. pylori infection, a direct link between Foxp3 and miR-155 in human T cells and highlights the significance of cAMP in this miR-155 induction cascade."


The microRNA miR-155 controls CD8+ T cell responses by regulating interferon signaling


microRNA-155 Regulates the Generation of Immunoglobulin Class-Switched Plasma Cells


Expression of miRNA 155, FOXP3 and ROR gamma, in children with moderate and severe atopic dermatitis.



"Atopic dermatitis is a disease characterized by a chronic inflammatory process in the skin, but its link to miRNA 155 is less known. The aim of the study was to evaluate the expression of microRNA155, and T helper type 17 cells and Treg cells in children with atopic dermatitis.


The study population consisted of: children seen for atopic dermatitis at the outpatient ambulatory of Dermatology at the Children Hospital Regina Margherita, Torino, Italy,( n = 23); healthy control subjects ( n =23). Blood samples were taken during routine control analysis and the expression of miRNA 155 and the production of FOXP3 and RORˠ was determined using PCR real time.


The analysis of miR-155 shows that the over-expression of miR-155 is statistically significant (p = 0.0040) in the group of patients with atopic dermatitis compared to the healthy control group. Analysis of mRNAs of FOXP3 and RORˠ shows a FOXP3 mRNA expression statistically higher in the group of patients (p = 0.0057). The Th17 / Treg ratio is significantly smaller in patients with atopic dermatitis (p = 0.0012). Also the ratio miR-155/Th17/Treg is larger in the group of patients with atopic dermatitis (p = 0.0002).


Our results suggest that increased miR-155 and FOXP3 and RORˠ responses may provide a link to immune dysregulation associated with atopic dermatitis. Although a point-by-point correlation between miR-155 and the ratio Th17/Treg is not demonstrated, our findings shows that these two elements do not appear to be completely unrelated to each other."


Cutting edge: the Foxp3 target miR-155 contributes to the development of regulatory T cells.


"Foxp3 is a transcription factor that is essential for the normal development of regulatory T cells (Tregs). In the absence of microRNAs (miRNAs), Foxp3(+) Tregs develop but fail to maintain immune homeostasis, leading to a scurfy-like disease. Global analysis of the network of genes regulated by Foxp3 has identified the miRNA miR-155, which is highly expressed in Tregs, as a direct target of Foxp3. In this study we report that miR-155-deficient mice have reduced numbers of Tregs, both in the thymus and periphery, due to impaired development. However, we found no evidence for defective suppressor activity of miR-155-deficient Tregs, either in vitro or in vivo. Our results indicate that miR-155 contributes to Treg development, but that additional miRNAs control Treg function."


The role of miR-155 in regulatory T cells and rheumatoid arthritis


MicroRNA-155 Promotes Autoimmune Inflammation by Enhancing Inflammatory T Cell Development


This last one makes me think impaired IL-17 in the gut may allow for Candida increases.

Impaired IL-17 Production in Gut- Residing Immune Cells of 5xFAD Mice with Alzheimer's Disease Pathology.


"Alzheimer's disease (AD) is characterized by accumulation of amyloid-β plaques that further promotes microglia-mediated neuroinflammatory responses and inflammation in the brain. Emerging data are revealing the relation between gut-associated lymphoid tissue (GALT) cells and CNS, as effector cells primed in the gut might home to the brain. This study aimed to determine cell composition of GALT in 5xFAD mice, an established model for AD. Immune cells isolated from Peyer's patches (PP) and mesenteric lymph nodes (MLN) were stained with surface and intracellular markers for T helper (Th) subpopulations, B lymphocytes and macrophages and analyzed cytofluorimetrically, while cytokine expression and production were determined by qPCR and ELISA, respectively. Inflammation was detected in GALT of 5xFAD mice with established AD pathology. Although the production of IFN-γ, IL-4, and IL-10 was comparable between the strains, lower IL-17 production was observed in PP and MLN cells. This phenomenon could not be attributed to a lower abundance of Th17 cells, or cytokines that initiate their formation or propagation (TGF-β, IL-6, and IL-23). Also, reduced IL-17 production was not a consequence of altered Il-17 mRNA transcription or deficiency of Rorγt, a key transcription factor for IL-17. However, the expression of miR-155 (a non-coding micro RNA that promotes the development of Th17 cells), was significantly lower in MLN cells of 5xFAD mice. In contrast, mice without AD neuropathology did not have inflammation in GALT or altered Th17 numbers, nor decreased IL-17 production. In conclusion, the observed changes in GALT of 5xFAD mice mirror the disease progression and might reflect inadequate immune surveillance in the gut and lead to enhanced AD pathology."



The mir55 info is very interesting, sitting at the juncture of all these chronic diseases which seem to keep intersecting each other.


This is likely involved in our case and degrees of it in others, but having discussed hyperemesis gravidarum in the past here and having long seen Helicobacter pylori as playing a role I had found this interesting. The second report one is notable too. If you have read the recent report on Natural Killer cells function in uterine fetus development the third report may show connections with the last report on Heme Oxygenase and it's impact on immune cells NK cells, T c& B cells.. {may be tying into Jaundice, biliverdin, bilirubin} The uterine NK cells also deal with the uterine lining to remove inflammation and also deal with pathogens. like bacteria.

Helicobacter pylori and pregnancy-related disorders


"Helicobacter pylori (H. pylori) infection is investigated in gastric diseases even during pregnancy. In particular, this Gram-negative bacterium seems to be associated with hyperemesis gravidarum, a severe form of nausea and vomiting during pregnancy. During the last decade, the relationship among H. pylori and several extra-gastric diseases strongly emerged in literature. The correlation among H. pylori infection and pregnancy-related disorders was mainly focused on iron deficiency anemia, thrombocytopenia, fetal malformations, miscarriage, pre-eclampsia and fetal growth restriction. H. pylori infection may have a role in the pathogenesis of various pregnancy-related disorders through different mechanisms: depletion of micronutrients (iron and vitamin B12) in maternal anemia and fetal neural tube defects; local or systemic induction of pro-inflammatory cytokines release and oxidative stress in gastrointestinal disorders and pre-eclampsia; cross-reaction between specific anti-H. pylori antibodies and antigens localized in placental tissue and endothelial cells (pre-eclampsia, fetal growth restriction, miscarriage). Since H. pylori infection is most likely acquired before pregnancy, it is widely believed that hormonal and immunological changes occurring during pregnancy could activate latent H. pylori with a negative impact not only on maternal health (nutritional deficiency, organ injury, death), but also on the fetus (insufficient growth, malformation, death) and sometime consequences can be observed later in life. Another important issue addressed by investigators was to determine whether it is possible to transmit H. pylori infection from mother to child and whether maternal anti-H. pylori antibodies could prevent infant’s infection. Studies on novel diagnostic and therapeutic methods for H. pylori are no less important, since these are particularly sensitive topics in pregnancy conditions. It could be interesting to study the possible correlation between H. pylori infection and other pregnancy-related diseases of unknown etiology, such as gestational diabetes mellitus, obstetric cholestasis and spontaneous preterm delivery. Since H. pylori infection is treatable, the demonstration of its causative role in pregnancy-related disorders will have important social-economic implications."


The choroid plexus epithelium as a novel player in the stomach-brain axis during Helicobacter infection.


"Several studies suggest a link between shifts in gut microbiota and neurological disorders. Recently, we reported a high prevalence of Helicobacter suis (H. suis) in patients with Parkinson's disease. Here, we evaluated the effect of gastric H. suis infection on the brain in mice. One month of infection with H. suis resulted in increased brain inflammation, reflected in activation of microglia and cognitive decline. Additionally, we detected choroid plexus inflammation and disruption of the epithelial blood-cerebrospinal fluid (CSF) barrier upon H. suis infection, while the endothelial blood-brain barrier (BBB) remained functional. These changes were accompanied by leakage of the gastrointestinal barrier and low-grade systemic inflammation, suggesting that H. suis-evoked gastrointestinal permeability and subsequent peripheral inflammation induces changes in brain homeostasis via changes in blood-CSF barrier integrity. In conclusion, this study shows for the first time that H. suis infection induces inflammation in the brain associated with cognitive decline and that the choroid plexus is a novel player in the stomach-brain axis."


This next one is quite good. While posting only the abstract I suggest reading it all.

Effects of heme oxygenase-1 on innate and adaptive immune responses promoting pregnancy success and allograft tolerance

"The heme-degrading enzyme heme oxygenase-1 (HO-1) has cytoprotective, antioxidant, and anti-inflammatory properties. Moreover, HO-1 is reportedly involved in suppressing destructive immune responses associated with inflammation, autoimmune diseases, and allograft rejection. During pregnancy, maternal tolerance to foreign fetal antigens is a prerequisite for successful embryo implantation and fetal development. Here, HO-1 has been implicated in counteracting the overwhelming inflammatory immune responses towards fetal allo-antigens, thereby contributing to fetal acceptance. Accordingly, HO-1 ablation negatively impacts the critical steps of pregnancy such as fertilization, implantation, placentation, and fetal growth. In the present review, we summarize recent data on the immune modulatory capacity of HO-1 towards allo-antigens expressed by the semi-allogeneic fetus and organ allografts. In this regard, HO-1 has been shown to promote alloantigen tolerance by blocking dendritic cell maturation resulting in reduced T cell responses and increased numbers of regulatory T cells. Moreover, HO-1 is suggested to shift the uterine cytokine milieu towards a protective Th2 profile and protects fetal tissue from apoptosis by upregulating anti-apoptotic molecules. Thus, HO-1 is not only a pivotal regulator of the initial steps of pregnancy; but also, an important player in supporting the maternal immune system in tolerating the fetus.


Looking at mir-155 effecting Osteoglycin. Osteoglycin is mentioned as being produced by NK cells in this last piece.

The body’s killer immune cells also feed fetuses in the womb

"The immune system’s aggressive natural killer cells – which normally kill cancer cells and infectious pathogens – also help nourish early fetuses, helping them grow.

This discovery was made by Zhigang Tian of the University of Science and Technology of China, in Hefei, and his team. Analysing natural killer cells from mice, they identified a subset that’s only produced in the uterus, and only during early pregnancy.

They named these “uterine NK cells”, and found that these cells produce large quantities of two proteins that are vital for growing fetuses.

One of these proteins, called pleiotrophin, drives the growth of blood vessels, bone, cartilage and brain fibres. The other protein, osteoglycin, orchestrates heart development and healthy growth of skin and eyes.

When the researchers examined womb tissue from 54 women, they found that those who had recently experienced miscarriages had fewer uterine NK cells than those who’d had successful pregnancies."




Close to 10 years ago I had researched that idea and ended up doing a protocol designed to handle intracellular pathogens. My wife was on Olmesartan for well over 4 years. The vitamin D issue is certainly not settled though pro D is ascendant. The Olmesartan does a lot more than activate the VDTR, it also blocks the AT1 receptor raises SOD and controls TNF-A and other cytokines.
Have posted about Autophagy a few times over the last few years in this thread.
Here is from 2013 I

nflammaging: disturbed interplay between autophagy and inflammasomes

Hve been down the MTOR path too for a good while, but the you tube speaker is on target as far as I have listened to him.


"Some authorities now believe that low 25(OH)D is a consequence of chronic inflammation rather than the cause. Research points to a bacterial etiology pathogenesis for an inflammatory disease process which results in high 1,25(OH)2D and low 25(OH)D. Immunotherapy, directed at eradicating persistent intracellular pathogens, corrects dysregulated vitamin D metabolism and resolves inflammatory symptoms."
(interesting flow chart illustrations to the study)

autophagy cure or curse, a lecture by Dr Steven Phillips, focused on neurodegenerative disease


You are correct about TB and Lipopolysaccharide. I had read that it did not have it on the outer wall when dormant. This aspect is new to me and I am trying to understand how LPS levels are raised in people with the levels attributed to a dormant bacteria. I had read; " nonreplicating cells do not synthesize new cell wall" in reference to TB. I did not make that clear at all.

I put the wrong substance in that last post too. It is Lipoarabinomannan, that is a component of the TB cell wall that elicits inflammation or heightens it. Either way, TB, mycoplasma, and Helicobacter pylori are infections that have been in my scope along with Strep. I had generally though at least a part of the lipopolysaccharide was coming through the leaky gut, but pathogens also in the rest of the system added to the mix.

Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes.


Low serum vitamin D levels in type 2 diabetes patients are associated with decreased mycobacterial activity.


This is an outside possibility of involvement.

TLR4-NOX2 axis regulates the phagocytosis and killing of Mycobacterium tuberculosis by macrophages.


Implication of Cytotoxic Helicobacter pylori Infection in Autoimmune Diabetes


Helicobacter pylori CagA antibodies and thyroid function in latent autoimmune diabetes in adults


and this that is just interesting...

Helicobacter pylori Infection and Graft-versus-Host Disease


{Autophagy has been connected to Autism}

Innate immunity to mycobacteria: vitamin D and autophagy.


"Autophagy is an ancient mechanism of protein degradation and a novel antimicrobial strategy. With respect to host defences against mycobacteria, autophagy plays a crucial role in antimycobacterial resistance, and contributes to immune surveillance of intracellular pathogens and vaccine efficacy. Vitamin D3 contributes to host immune responses against Mycobacterium tuberculosis through LL-37/hCAP-18, which is the only cathelicidin identified to date in humans. In this review, we discuss recent advances in our understanding of host immune strategies against mycobacteria, including vitamin D-mediated innate immunity and autophagy activation. This review also addresses our current understanding regarding the autophagy connection to principal innate machinery, such as ubiquitin- or inflammasome-involved pathways. Integrated dialog between autophagy and innate immunity may contribute to adequate host immune defences against mycobacterial infection."



so perhaps its not specifically the latency, as much as, or in addition to ability of some bacteria to subvert autophagy (remove abnormal proteins) eg bartonella, brucellosis and coxiella (borreliosis unknown).


I am not sure what you mean by production of lipopolysaccharide, but TB is like all gram negative bacteria, and lipopolysaccharide is very much present as the outer coat of that bacteria too?

TB or TB like bacteria does seems to keep showing up both in literature and in our own back yards. .

I thought TB was very much taken care of and not so much because of antibiotics, but by pasteurizing the milk.

Even with antibiotics - what happens is that the TB bacteria is never gotten rid of. The patient that is considered cured, still has it. The antibiotic just helped the patient's body to encapsulate or encase the bacteria. So a person that once had TB still has an encapsulated bacteria still within their lungs.

This fall there has been a huge number of deer dying in the woods from a wasting disease from a bacteria some what like TB, if not TB. Some times I do wonder if they really can figure out different variants of microbes, or even able to figure out what they can morph into.

This was in Kentucky. IT was so bad that the woods, waffled with the stench of rotting meat. This was here in Kentucky. But my child hood friend up in Michigan said it was the same thing gong on up there. That one farmer with a large farm had around 80 head of cattle come down with it, and the deer around his farm had it too.

We our own selves had four cows die of a wasting disease; even though the vet said old age. Hmmmm, don't think I believe that? Some of our cattle showed lameness in the back hips, then loss of weight. All regain their vigor and strength during the summer and although I agree that they were old ; they still were having calves. However; one of the younger cows were salivating extensively this spring and even though she is okay now, I think she is still on the thin side. I don't think she is going to have a calf this year, she does not look like it.

There was a cycle going on, that involve midges, water borne sucking little insects.

We ran over two baby deer this summer in our hay field. Twins, I felt really bad about it, but it was an accident and could not be helped. However it shows you just how there is contact between cattle, deer, water, food out there. Cattle of course we are closely linked to also.

There was a very well written article - I forgot the author and such, but it can be found on the internet that the prions they found in the brains of the victims of mad cow disease were really remnants of the TB bacteria. It may be that there are no such thing as prions, that is still just a theory. I have looked at it and I do know that in Organic Chemistry there was left and right molecules and it could throw a wrench some of the chemical reactions - I just don't see how they can make more of themselves? How can proteins take on what we consider the definition of life and can reproduce; make more of themselves? It makes more sense that Prions instead may be more of a signs of a slow growing; few and far between, very missed pathogenic bacteria.

And what does it take to kill these stealthy bacteria if that is true.
There was an article a while back that was sounding the alarm that the deep brain probes they were using on patients that turned out to have some kind of form of mad cow disease - were spreading to other patients that did not . Even though they were cleaning the probes between procedures apparently what they thought was disinfecting the probes was not enough to kill the prions- proteins with molecules turned the wrong way. Perhaps it was not enough to kill a few undetected bacteria.


For other reasons I had felt it could not be TB and while TB does evoke lipopolysaccharide-binding protein and bind to it TB does not produce lipopolysaccharide which is stated to be elevated in those with the bacteria.



I would believe so, given their persistence and dormancy, but many types of bacteria can become dormant. It does not speak of spores or allude to pleomorphic bacteria, so that is a mystery. It surely isn't tb, but tb fits somewhat as it is very slow growing and can become latent and tb has some connections with diabetes.. I don't know why the full report did not say anything more about the bacteria as they seem to imply they have isolated it. Either it is an unknown type or they want to keep the information to themselves at this point. I thought it interesting they mention leaky gut as that is how we see some problems coming about and I have been curious about such a pathogen for a long time.

Here is one quote. from the paper linked below.

""T2D is accompanied by long-term inflammation, and this inflammation is mediated in part by increased fibrinogen levels, as well as a changed cytokine profile that is driven, at least in part, by dysregulated glucose and insulin function. The origin of this inflammation is mostly unclear and remains unresolved in diabetes. It is known that gut dysbioses and atopobioses71 (colloquially referred to as ‘leaky gut’) are a well-known contributor to the pathogenesis of many metabolic diseases, including obesity146, T1D147, 148, T2D146, 149, 150, and CVD151. We have previously suggested that there is a fundamental link between gut dysbioses, the presence of a (dormant) blood microbiome and the presence of the highly inflammatory LPS71""

Lipopolysaccharide-binding protein (LBP) reverses the amyloid state of fibrin seen in plasma of type 2 diabetics with cardiovascular co-morbidities



saw your post about Pretorius and Kell.
does this point toward the slower dividing bacteria, longer latencies?


T clarify the TRP-P8 or TRP-M8 Gene is involved and connected it is just not the one I was mentioning when I said P8 gene. I am referring to the entry 3 posts back.


A little more elaboration of the immune connections of Autism-immune function-and mir-155 and Pten. {Particularly pointed out here: Psoriasis}

MiR-155 promotes cell proliferation and inhibits apoptosis by PTEN signaling pathway in the psoriasis.

"MicroRNAs (miRNAs) have been demonstrated to contribute to malignant progression in psoriasis development. The purposes of the study was to evaluated the effects of miRNA-155 on cell proliferation, migration and apoptosis in psoriasis development via PTEN singaling pathway and identify its direct target protein. Quantitative real-time RT-PCR (qRT-PCR) was performed to examine the level of miR-155 in psoriasis cells, miR-155 was downregulated in a psoriasis cell line Hacat by transfected with small interfering RNA (siRNA), respectively. Cell survival was detected by the MTT assay and colony formation assay. Cell migration and invasion were measured via wound-healing assayand transwell assay. In addition, cell cycle and apoptosis about psoriasis cells was measured by flow cytometry. In this study, qRT-PCR assay showed that the expressions of miR-155 mRNA in psoriasis tissues were significantly higher than that in normal tissues. The assays about cell growth and proliferation showed that miR-155 knockdown led to a significant decrease in cell proliferation which was determined by MTT assay and colony formation assay compared to those of Lv-NC cells. Flow cytometry analysis showed that depletion of miR-155 could cause cell cycle change and the number of apoptotic cells was significantly increased in Lv-miR155 cells compared with control cells. In addition, the expression of several apoptosis-related factors were dramatically changed, such as PTEN, PIP3, AKT, p-AKT, Bax and Bcl-2. Our findings indicate that down-regulation of miR-155 significantly inhibits proliferation, migration, invasion and promotes apoptosis through PTEN singaling pathway in psoriasis cells. miR-155 might function as an oncogene miRNA in the progress of psoriasis."


Immune Mediated Conditions in Autism Spectrum Disorders


"We conducted a case-control study among members of Kaiser Permanente Northern California (KPNC) born between 1980 and 2003 to determine the prevalence of immune-mediated conditions in individuals with autism, investigate whether these conditions occur more often than expected, and explore the timing of onset relative to autism diagnosis. Cases were children and young adults with at least two autism diagnoses recorded in outpatient records (n=5,565). Controls were children without autism randomly sampled at a ratio of 5 to 1, matched to cases on birth year, sex, and length of KPNC membership (n=27,825). The main outcomes - asthma, allergies, and autoimmune diseases - were identified from KPNC inpatient and outpatient databases. Chi-square tests were used to evaluate case-control differences. Allergies and autoimmune diseases were diagnosed significantly more often among children with autism than among controls (allergy: 20.6% vs. 17.7%, Crude odds ratio (OR) = 1.22, 95% confidence interval (CI) 1.13 – 1.31; autoimmune disease: 1% vs. 0.76%, OR = 1.36, 95% CI 1.01 – 1.83), and asthma was diagnosed significantly less often (13.7% vs. 15.9%; OR = 0.83, 95% CI 0.76 – 0.90). Psoriasis occurred more than twice as often in cases than in controls (0.34% vs. 0.15%; OR =2.35, 95% CI 1.36 – 4.08). Our results support previous observations that children with autism have elevated prevalence of specific immune-related comorbidities."



Note this speaks about gene expression. There are other interesting points in the report I have not quoted. {reference to gliadin is one}

Streptococcal infection-related autoimmunity and autism: crosstalk in protein functional networks

Genes of note
"Many ASD-associated genes are particularly expressed and associated within the IS include, APP, BCL11A, KLC1, ETS1, MET, IL1RN, NDRG1, NGF, TNF and VEGF (Table 5). These genes are receptors (APP, MET, IL1RN), involved in angiogenesis (NDRG1, VEGF), cell maintenance and development (BCL11A, KLC1, NGF,) and inflammation (ETS1, TNF). APP, ETS1, TNF and VEGF may be of a particular interest. APP encodes for the amyloid beta precursor protein, which is highly expressed in neurons and glial cells [49-51]. However, APP products also have a functional role, including synaptic adhesion, neuroprotective properties and antimicrobial functions [52-54]. APP transport in the brain is mediated by subunits formed by KLC1 molecules [55]. ETS1 encodes for ETS proto-oncogene 1, a transcription factor that has roles in inflammation and chemokine and cytokine activation particularly in endothelial cells and links to reactive microglia [56,57]. ETS-1 has been shown to co-localise with VEGF, TNF and APP products in the brain [57]. Vascular endothelial growth factors (VEGF) are a family associated with endothelial cell regulation and angiogenesis, even influencing the blood-brain barrier (BBB) [58,59]. Notably, VEGF appears to be able to alter the permeability of the BBB, and can increase permeability and cause breakdown [59-61]. Tumour necrosis factor (TNF) is a proinflammatory cytokine and is implicated in numerous functions and pathologies. TNF is implicated in inflammation and can affect the permeability of the BBB [62]. Of the streptococcal-associated genes, autoantibody targets MAG and MBP are the most prominent. MAG encodes for myelin-associated glycoprotein, a membrane protein that inhibits nerve regeneration [63]. MBP encodes for myelin basic protein, which is a major protein of the myelin sheath and has a regulatory role in myelination [64].

Potential mechanism

Our vision of how streptococcal infections can cause ASD in children is presented in Figure 7. Alterations in ETS1, TNF or VEGF functions, or their combination can decrease the permeability of the BBB and leave an individual vulnerable to toxic or autoimmune components developed due to an infection. Mutations may not act directly upon these genes but may affect their expression and protein proliferation [65,66]. This may be a result of mutations in promoter regions or polymorphisms in cytokines (TNF) or may be an upstream molecule [67-69]. VEGF and ETS1 have been associated with TNF in Alzheimer’s disease [57]; therefore, we can conceive that they work functionally together in the brain. ETS1 and VEGF can induce microglial activity towards increased TNF production [57,70-72]. Additionally VEGF expression in astrocytes, a component of the BBB, can induce the BBB breakdown [73], supported by a streptococcal- induced inflammation. Streptococcal infections produce autoantibodies against MAG and MBP. With a weakened BBB, anti-MAG and anti-MBP can travel across and target developing neurones for destruction by immune cells able to cross the weakened BBB. In fact, thinner myelination has been reported in some areas of the brain in ASD, such as the orbitofrontal cortex (OFC), as well as a high density of thinly myelinated neurons when compared to controls [74]. OFC abnormalities have already been associated with ASD and it is speculated that a decrease in myelin may mean that longer axons that provide the cross talk for emotion-based behaviors are less efficient [75,76]. From the other hand, neurite overgrowth found in ASD patients [77,78] may be explained by MAG (inhibitor of neurite regrowth) immuno- inhibition."


From published and our study it is clear that there is overlap within the IS and NS functions that may be responsible for synergism in inheritable and environmental components in aetiology of a number of neuro-psychiatric disorder, and ASD, in particular. APP, BCL11A, KLC1, ETS1, MET, IL1RN, NDRG1, NGF, TNF, VEGF, HSPD1, MAG and MBP proteins are likely candidates to affect susceptibility to the environmental component. What is notable is that many of these genes were identified to have roles in the developing brain, reflecting the paediatric nature. Despite a proposed theory (Figure 7), uncertainties remain as to how some of these genes may interact to affect ASD. We suggest that APP, HSPD1, MET and NDRG1 may be implicated in the reaction caused by the autoantibodies. Those would be ideal candidates to investigate further using experimental methods in animal models or to be tested for in cases of PANDAS or more profound ASD cases in children."



A personal correction I have long ignored. I don't know if any have see a holistic connection of all the things I have posted though a couple of associations I posed never panned out. Yet, I posted one clear error and only have my indiscretion to thank for doing so.

This association did prove fruitful, but not via the gene I listed as a description. I posted this:

"Transforming growth factor beta-1 enhances Smad transcriptional activity through activation of p8 gene expression.


I then listed this which is not associated .
TRP-P8 Gene Card

It is rather elucidated through these reports.

Transforming growth factor beta-1 enhances Smad transcriptional activity through activation of p8 gene expression.


and this:

The human NUPR1/P8 gene is transcriptionally activated by transforming growth factor β via the SMAD signaling pathway.


and possibly this:

NUPR1 interacts with p53, transcriptionally regulates p21 and rescues breast epithelial cells from doxorubicin-induced genotoxic stress.


P53 is a player.

Autism multiplex family with 16p11.2p12.2 microduplication syndrome in monozygotic twins and distal 16p11.2 deletion in their brother

"The results of the SNP arrays were confirmed by qPCR (Figure 2b). In patients 2 and 3, the qPCR confirmed the duplication of VWA3A located at 16p12.1, and NUPR1, LAT, and ALDOA located at 16p11.2, with normal dosage of the genes flanking the rearranged region. In patient 1 and the father, both NUPR1 and LAT were deleted."

"Of the other eight genes contained in the minimal deleted region, three are involved in autosomal recessive disorders (TUFM, ATP2A, CD19), three are involved in immunity (NFATC2IP, LAT, ATXN2L), RABEP2 has a role in membrane trafficking, and little is known about the function of SPNS1 (Supplementary Table 4). SH2B1 haploinsufficiency, already implicated in central nervous system-mediated obesity,24 could also participate in neurodevelopmental and other phenotypes. The widely expressed scaffold protein SH2B1 binds to a variety of ligand-activated receptor tyrosine kinases, including the receptors for nerve growth factor, insulin and insulin-growth factor 1. SH2B1 facilitates glial-cell-line-derived neurotrophic factor-induced neurite outgrowth through RET receptor signaling.28 Through its implication in the RET-glial-cell-line-derived neurotrophic factor signaling pathway, SH2B1 could also have a role in the abnormalities of renal morphogenesis and enteric innervation seen in patients with distal 16p11.2 deletions.26"


I don't think this will matter to most, but I wanted to set it straight.


Just a bit on mir-155. Many others mir's have their part, but this one is particularly involved. It is a inflammatory mediator. When I found it effected the blood brain barrier the other things I had learned about mad a lot more sense. A lot to learned from the reports in the sidebar, pls reading all of these two reports.

miR-155 Is Essential for Inflammation-Induced Hippocampal Neurogenic Dysfunction


"Peripheral and CNS inflammation leads to aberrations in developmental and postnatal neurogenesis, yet little is known about the mechanism linking inflammation to neurogenic abnormalities. Specific miRs regulate peripheral and CNS inflammatory responses. miR-155 is the most significantly upregulated miR in primary murine microglia stimulated with lipopolysaccharide (LPS), a proinflammatory Toll-Like Receptor 4 ligand. Here, we demonstrate that miR-155 is essential for robust IL6 gene induction in microglia under LPS stimulation in vitro. LPS-stimulated microglia enhance astrogliogenesis of cocultured neural stem cells (NSCs), whereas blockade of IL6 or genetic ablation of microglial miR-155 restores neural differentiation. miR-155 knock-out mice show reversal of LPS-induced neurogenic deficits and microglial activation in vivo. Moreover, mice with transgenic elevated expression of miR-155 in nestin-positive neural and hematopoietic stem cells, including microglia, show increased cell proliferation and ectopically localized doublecortin-positive immature neurons and radial glia-like cells in the hippocampal dentate gyrus (DG) granular cell layer. Microglia have proliferative and neurogenic effects on NSCs, which are significantly altered by microglial miR-155 overexpression. In addition, miR-155 elevation leads to increased microglial numbers and amoeboid morphology in the DG. Our study demonstrates that miR-155 is essential for inflammation-induced neurogenic deficits via microglial activation and induction of IL6 and is sufficient for disrupting normal hippocampal development."


microRNAs as novel regulators of angiogenesis

"As mentioned before, numerous factors are implicated in vessel growth. Among these factors, angiotensin II (Ang II), the main effector peptide of the renin-angiotensin system, appears to be implicated in the regulation of the angiogenic process92. ANG II has been shown to work through both type 1 (AT1R) and type 2 (AT2R) receptors, which display opposing vasomotor and angiogenic actions93. AT1R receptor activation is known to stimulate vascular growth and microvascular angiogenesis in nonneural tissues such as skeletal and cardiac muscle, whereas AT2R activation was recently shown to antagonize these actions94. miR-155 is expressed in ECs and VSMC20,95 and has been shown to specifically interacts with the 3′UTR of the human AT1R mRNA, thereby reducing the endogenous expression of the hAT1R and consequently Ang II signaling95. Translational repression by miR-155 provides yet another mechanism by which AT1R expression can be modulated. In this regard, it has been reported that Ang II induces in a dose dependent manner the expression VEGFR2 and significantly enhances VEGF-induced cell proliferation and tube formation, mediated by AT1 receptor96 and suggesting that AT1 receptor may contribute to the development of diabetic retinopathy by enhancing VEGF-induced angiogenic activity. Then, the downregulation of AT1R by miR-155 suggest an antiangiogenic function for this miRNA in ECs. However, its role in EC angiogenesis has not been specifically addressed. Stimulation of human fibroblast with transforming growth factor β-1 (TGF-β1) decreased the expression of miR-155 and increased the expression of hAT1R. Furthermore, miR-155 is induced in macrophages by cytokines such as tumor necrosis factor α (TNF α) and interferon β (IFNβ)97. Interestingly, angiogenic stimulation of EC with VEGF increases the expression of miR-15520 suggesting VEGF may control the levels of ATR1 via miR-155. Nevertheless, the oncogenic potential of miR-155 has been confirmed in mice, where its overproduction leads to spontaneous B-cell malignancy, showing the complexity of miRNA-mediated regulation, given that the same miRNA may have opposite effects in different biological contexts."



God is Love. Jesus is Lord.


For my satisfaction. Scientific reports will never approach what I have experienced and understood, so screw it. Proof 80 percent.


Having a retro phase after mentioning methionine two posts back. The research that followed led information about these matters as succinctly put on 2005 in the link below. I need to keep these things in mind. Many of you know this I am sure.

The Glutathione/Sulfation/Methylation Pathway



Since there are various routes to Autism this stands out as a curious possible connection to Hep B. I included the first report in an entry in this forum in 2013. The increased expression of Foxp1 in those with Autism in the second study makes the first report's reference to different hep b vaccine responses associate with the Foxp1 in those with Autism I don't know by what mechanisms there would be interaction except through B cell effects. Mutations of Foxp1 are associated with low numbers of Autism and high expression is found in many with Autism. I will try to see if there is a connection, but maybe someone else may know something.

New genetic associations detected in a host response study to hepatitis B vaccine.


This report is best fully read.

Increased gene expression of FOXP1 in patients with autism spectrum disorders

"The FOXP1 gene encodes a member of the forkhead box transcription factor family that contains a DNA-binding domain and a protein-protein interaction domain. The FOXP1 gene functions as a transcription repressor [39, 41, 42], and is widely expressed in the developing and mature brain. The gene has been suggested to be involved in the development and function of the brain [41, 43]. In the literature, three subjects with mental retardation and significant language and speech deficits were detected to have heterozygous deletions overlapping the FOXP1 gene [44]. Two mentally retarded individuals with autistic features were detected to have a de novo intergenic deletion and a de novo nonsense mutation in the FOXP1 gene, respectively [45]. In an exome sequencing study of 20 sporadic ASD patients (simplex ASD), a de novo single-base insertion in FOXP1 that introduces a frameshift and a premature stop codon was identified in a severely affected patient [46]. These data suggest that haploinsufficiency or hypomorphic mutations of FOXP1 with reduced expression or deficient activity of FOXP1 are associated with syndromic or non-syndromic ASD. However, these FOXP1 mutations associated with ASD are rare; they may not apply to the pathogenesis of autism in general. In the present study, we found that increased FOXP1 gene expression was associated with autism in general. Our finding may expand our understanding about the relationship of FOXP1 with autism.

FOXP1 protein was known to interact with another subfamily member FOXP2 to form a heterodimer and co-expressed with FOXP2 in several brain regions, suggesting close functional collaboration between the two proteins [39, 40]. Contactin-associated protein-like 2 (CNTNAP2), a neurexin family protein that functions as a neuronal adhesion molecule and receptor, was found to be a direct neural target bound by human FOXP2 protein [47]. Mutations of FOXP2 and CNTNAP2 were linked to speech and language disorders and ASD [36, 37, 38, 48, 49, 50, 51]. Taken together, these data indicate that interactions among FOXP1, FOXP2, and CNTNAP2 genes may play an essential role underlying the pathogenesis of syndromic and non-syndromic ASD.

In a more recent study, forkhead box protein p1 was found to function as a transcriptional repressor of immune signaling in the mouse brain, and was involved in the pathophysiology of Huntington’s disease [52]. The study suggested that Foxp1-regulated pathways might be important mediators of neuronal-glial cell communication. Thus, the increased FOXP1 gene expression in the LCL of ASD patients as found in this study may offer a new insight that dysregulated immune signaling in the brain contributes to the pathogenesis of ASD."



Good to have you drop a line Benedetta. Yes, I went back and found my original research from many years ago about B vitamins and folate and our information agrees. I slipped into vitamin no mans land, but again remembered the interaction of b, folate and these matters. In our case sulpha drug gave a manifestation of phenylic sensitivity and PST/sulfate issues. Here is an email I received back from Dr. Shaw of Great Plains Lab about a question I had sent him back in 96.

Sulfur - Phenols and Phenolsulfotransferase

These drug interactions involving phenytoin,trimethoprim {Nick's note-Bactirm contains trimethoprim}, and sulfa drugs are extremely complex and unfortunately there is no easy answer for the reason for sensitivity to a particular drug. All of these drugs inhibit folic acid metabolism or transport, all of them may elicit allergic type reactions, all have complex routes of metabolic tranformation that may affect one another, and all of these may be metabolized by PST. Two of the drugs may have significant effects because of their antimicrobial action which changes the biochemistry of the GI tract by removing different groups of microorganisms.

William Shaw PhD

Dear Nick,

I have received the following answer to your question about sulfa drugs from Dr. Sinaiko, one of our

medical advisors:

Subject: Re:sulfonamides

Sulfonamides do, of course, contain sulfur in their chemical formulae.

Some brands will contain phenolic dyes.

I hope that has answered your question. If you need more information, feel free to ask.

Best wishes,

Hi all,

Many days ago, I have asked about cysteine, homocysteine (methionine) metabolism might be one of the possible link to seizures and neural disorders. I found one article about cysteine metabolism abnormality can link to phenolic metabolism abnormality.

Phenotypic variation in xenobiotic metabolism and adverse environmental response: focus on sulfur-dependent detoxification pathways.

McFadden SA

Independent Research Advocates, Dallas, TX 75206, USA.

Toxicology 111: 43-65 (1996)


Proper bodily response to environmental toxicants presumably requires proper function of the xenobiotic (foreign chemical) detoxification pathways. Links between phenotypic variations in xenobiotic metabolism and adverse environmental response have long been sought. Metabolism of the drug S-carboxymethyl-L-cysteine (SCMC) is polymorphous in the population, having a bimodal distribution of metabolites, 2.5% of the general population are thought to be nonmetabolizers. The researchers developing this data feel this implies a polymorphism in sulfoxidation of the amino acid cysteine to sulfate. While this interpretation is somewhat controversial, these metabolic differences reflected may have significant effects. Additionally, a significant number of individuals with environmental intolerance or chronic disease have impaired sulfation of phenolic xenobiotics. This impairment is demonstrated with the probe drug acetaminophen and is presumably due to starvation of the sulfotransferases for sulfate substrate. Reduced metabolism of SCMC has been found with increased frequency in individuals with several degenerative neurological and immunological conditions and drug intolerances, including Alzheimer's disease, Parkinson's disease, motor neuron disease, rheumatoid arthritis, and delayed food sensitivity. Impaired sulfation has been found in many of these conditions, and preliminary data suggests that it may be important in multiple chemical sensitivities and diet responsive autism. In addition, impaired sulfation may be relevant to intolerance of phenol, tyramine, and phenylic food constituents, and it may be a factor in the success of the Feingold diet. These studies indicate the need for the development of genetic and functional tests of xenobiotic metabolism as tools for further research in epidemiology and risk assessment.

Yoshihisa Masuda

(Biotechnologist, Organic Chemist)

Also Ihave been looking for the element of the pathogen related to inflammation and the LPS source beyond that from a Leaky Gut, also the question arises as to why these cell walled pathogens gain a foot hold and are not destroyed by the immune system. I think Marshall's take and mycoplasma inhibit the immune system. anyway. Here is the report.

Bacterial cell wall mopping agents could treat chronic inflammatory diseases like type 2 diabetes

"Bacteria may be responsible for more than we suspect. Especially when it comes to inflammatory diseases such as type 2 diabetes.

Prof. Resia Pretorius from Stellenbosch University (SU) in South Africa and Prof. Douglas Kell from The University of Manchester have conducted a series of studies that are drastically changing the way scientists think about the effect bacteria have on a number of diseases including Alzheimer's disease, Parkinson's disease, Sepsis, Rheumatoid Arthritis, and most recently type 2 diabetes (T2D).

Previously, Pretorius and Kell have established that these chronic inflammatory diseases also have a microbial origin. "If the bacteria were active, or replicating, as in the case of infectious diseases, we would have known all about that," says Kell. "But the microbes are not replicating, they're mainly actually dormant."

Because their dormant nature meant that they did not manifest under standard microbial test conditions, bacteria were previously thought to be absent from human blood, consistent with the view that blood is 'sterile'. However, high levels of iron in blood (typical of inflammatory diseases) can effectively bring these bacteria back to life. Previous research suggested that under these conditions, the bacteria start replicating and secreting lipopolysaccharides (LPS), leading to increased inflammation.

The one thing these chronic diseases have in common is constantly elevated levels of inflammation. Pretorius and Kell had already established that anomalous amyloidogenic blood clotting, a cause of inflammation, is linked to and can be experimentally induced by bacterial cell wall constituents such as LPS and Lipoteichoic acid (LTA). These are cell wall components of Gram-negative and Gram-positive bacteria, respectively.

These coagulopathies (adverse blood clotting) are also typical of inflammatory diseases and the researchers have long shown that they lead to amyloid formation, where the blood clotting proteins (called fibrinogen) are structurally deformed from a-helixes to a flat b-sheet-like structures, potentially leading to cell death and neuro-degeneration.

As a result, the fibrin fibres of blood clots in diseased individuals are distinctly different from those of healthy individuals. This can be visualised microscopically and is discussed in various publications from the group. "In normal blood clots, these fibres would look like a bowl of spaghetti" explains Pretorius. "But in diseased individuals, their blood clots look matted with large fused and condensed fibres. They can also be observed with special stains that fluoresce in the presence of amyloid."

The researchers found that this changed clot structure is present in all inflammatory conditions studied, now including type 2 diabetes. But what is the link between this abnormal clot formation, bacteria, LPS and TLA? And are there any molecules that may "mop up" LPS or LTA and that might be circulating in the blood of people with inflammatory diseases?

In their 2017 study, recently published in Scientific Reports (a Nature publication), Pretorius and Kell, along with MSc student Ms Sthembile Mbotwe from the University of Pretoria, investigated the effect of LPS-binding protein (LBP), which is normally produced by all individuals. They added LBP to blood from T2D patients (and also to healthy blood after the addition of LPS). Previously they had showed that LPS causes abnormal clot formation when added to healthy blood, and that this could be reversed by LBP. In this publication they showed that LBP could also reverse the adverse clot structure in T2D blood. This process was confirmed by both scanning electron microscopy and super-resolution confocal microscopy. The conclusion is clear: bacterial LPS is a significant player in the development and maintenance of T2D and its disabling sequelae.

"In an inflamed situation, large amounts of LPS probably prevent LBP from doing its work properly," explains Pretorius.

So what does this mean in terms of treatment?

"We now have a considerable amount of evidence, much of it new, that in contrast to the current strategies for attacking T2D, the recognition that it involves dormant microbes, chronic inflammatory processes and coagulopathies, offer new opportunities for treatment," the researchers conclude. "


There was a study done that included around 5500 people.
Vitamin Bs did lower the occurrence of strokes.
However; if a stroke did occur it did not make any difference in how severe those strokes could be even if you were taking the B vitamins.

I thought they meant a regular B complex. Oh how I wish it was that simple

What they were taking as folic acid, B 6 and B12.

I am trying to reduce the pills my family is taking.
Also the amount of folic, B6 and B12 were rather high. I need to look at that study again if I can find it.

Oh, and a VA doctor told Dad back 15 years ago that he had Parkinsons.
We finally got around to going to see a neurologist today. Apparently Dad had a stroke 15 years ago, all following soon after a flu shot.

Apparently there are things that are Parkinson like, injuries to the brain. His was in the basal ganglia, and damaged some of the dopamine producing cells. That is how I understood it.


Thanks Visitor. B 6


Vitamin B6 prevents IL-1β production by inhibiting NLRP3 inflammasome activation


"Vitamin B6 includes six water-soluble vitamers: pyridoxal (PL), pyridoxamine (PM), pyridoxine (PN), and their phosphorylated forms. Pyridoxal 5'-phosphate (PLP) is an important cofactor for many metabolic enzymes. Several lines of evidence demonstrate that blood levels of PLP are significantly lower in patients with inflammation than in control subjects, and that vitamin B6 has anti-inflammatory effects, with therapeutic potential for a variety of inflammatory diseases. Although one of our group (NK) previously demonstrated that PL inhibits the NF-κB pathway, the molecular mechanism by which vitamin B6 suppresses inflammation is not well understood. Here, we showed that both PL and PLP suppressed the expression of cytokine genes in macrophages by inhibiting TLR-mediated TAK1 phosphorylation and the subsequent NF-κB and JNK activation. Furthermore, PL and PLP abolished NLRP3-dependent caspase-1 processing and the subsequent secretion of mature IL-1β and IL-18 in LPS-primed macrophages. In contrast, PM and PN had little effect on IL-1β production. PLP, but not PL, markedly reduced the production of mitochondrial reactive oxygen species (ROS) in peritoneal macrophages. Importantly, PL and PLP reduced the IL-1β production induced by LPS and ATP, or by LPS alone, in mice. Moreover, PL and PLP protected mice from lethal endotoxic shock. Collectively, these findings reveal novel anti-inflammatory activities for vitamin B6, and suggest its potential for preventing inflammatory diseases driven by the NLRP3 inflammasome."


B6 alone taxes PST though.


A similar event, some triggered by MMR, may effect the gut and induce cytokines production and bbb permeability with a flow of T Cells effecting the vessels and areas mentioned in this report. I don't know if Tcells in peripheral circulation would lower due to this occurring, but it would be interesting to know. This does not speak directly to Autism and gastro interaction and details mortality due to gastro dysfunction in mice, it sounds like it shares some of the pathology for many.

Very worthwhile.

Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit

Moreover, neutralization of the Th1 cytokine, interferon-gamma (IFN-γ), or that of the Th17 cytokine, IL-17A, also inhibited the brain micro-inflammation at the specific vessels (Figure 4E). Importantly, the accumulation of IL-17A- or IFN-γ-deficient pathogenic CD4+ T cells was significantly reduced at the specific blood vessels under stress conditions and resulted in less mortality (Figure 4—figure supplement 3). These data suggested that both IFN-γ and IL-17A from pathogenic CD4+ T cells are necessary for the accumulation at specific vessels and the severe phenotypes. Consistent with these results, prominent inhibitory effects on the disease development were observed with combined neutralization of IL-17A and IFN-γ(Figure 4F). These results suggested that stress-mediated CCL5 expression at the specific vessels induces the accumulation of pathogenic CD4+ T cells, particularly Th17 and Th1 cells and MHC class IIhiCD11b+ cells to establish brain micro-inflammation, which is critical for the development of fatal gastrointestinal failure. We call this phenomenon the stress-gateway reflex.

Brain micro-inflammation at specific vessels is sufficient to induce fatal gastrointestinal failure under stress condition

"We next investigated whether brain micro-inflammation at the specific vessels is sufficient to develop intestinal failure in mice under stress. To answer this question, we directly microinjected pathogenic CD4+ T cells plus MOG-pulsed DC or inflammatory cytokines, such as IFN-γ plus IL-17A or IL-6 plus IL-17A, either of which is known to be expressed by pathogenic CD4+ T cells and enhance chemokine expression at specific vessels in gateway reflexes previously identified (Arima et al., 2012; Sabharwal et al., 2014), at specific vessels of the boundary region of the third ventricle region, thalamus, and dentate gyrus under stress condition. We found that brain micro-inflammation induced by these treatments developed severe gastrointestinal failure and affected mortality (Figure 4G). Furthermore, we investigated the mortality of mice with microinjections of cytokines at the specific vessels under stress condition in the presence or absence of anti-CCL5 antibody treatment and found anti-CCL5 antibody treatment had no significant effect (Figure 4—figure supplement 4). This result suggested that CCL5 mainly contributes to the accumulation of immune cells including pathogenic CD4+ T cells at the specific vessels, while the effect of cytokine injection is CCL5-independent. These results suggest that brain micro-inflammation at the specific vessels, which is triggered by CCL5-mediated pathogenic CD4+ T cell accumulation, induces regional cytokine increment followed by severe gastrointestinal failure under stress condition."...

"Flow cytometry analysis confirmed an abundance of immune cell accumulation including pathogenic CD4+ T cells and MHC class IIhiCD11b+ cells in the hippocampus and interbrain area, where the specific vessels were localized (Figure 3C). Td-tomato labeling of microglia cells, which we used previously (Arima et al., 2015), revealed that MHC class IIhiCD11b+ cells originated from the peripheral organs rather than resident microglia cells (Figure 3D), suggesting that the MHC class IIhiCD11b+ cells that accumulated at the specific vessels were activated monocytes from the peripheral organs. Moreover, we found that various immune cells, including CD8+ T cells, B cells, NK cells, and neutrophils, had also accumulated at the specific vessels (Figure 3—figure supplement 2). Thus, the stress condition induced brain micro-inflammation at specific vessels of the boundary area of the third ventricle region, thalamus, and dentate gyrus in the transfer EAE model."



HMGB1, Autism, Kawasaki's

High-mobility group box 1 (HMGB1) in childhood: From bench to bedside

Autistic disorders
"Autism is a neurodevelopmental disability characterized by
impairments in verbal communications, reciprocal social in-
teractions, and restricted repetitive stereotyped behaviors [84].
Dysregulated immune function is a recurrent finding, includ-
ing evidence of brain reactive antibodies, altered cytokine levels
in the brain, and altered function of innate immune cells [96].
HMGB1 receptors are involved in the pathophysiological
mechanisms of autism. Enstrom et al. described abnormal sen-
sitivity of peripheral blood monocytes, isolated from children
with and without autism, to TLR ligands, suggesting a dysfunc-
tion in monocyte pathogen recognition and/or TLR signaling
pathways [43]. Junaid et al. showed high incidence of A-allele
homozygosis in the GLO1 gene, with reduction in Glo1 activity
[61]. This condition determines an accumulation in the brain of
methylglyoxal, leading to the formation of advanced glycosyl-
ated end products (AGE), which ultimately induces the RAGE-
mediated downstream signaling cascade [13]. Autistic children
are also characterized by abnormal serum levels of HMGB1
when compared with healthy controls [42].
High serum levels of HMGB1 may be a biomarker of the
impaired reciprocal social interactions in this
neurodevelopmental disorder."

Kawasaki disease
"Kawasaki disease (KD) is an acute, self-limited vasculitis,
with potential cardiovascular complications, developing in ∼
15 to 25 % of untreated children [79].
Hoshina et al. measured HMGB1 levels in 27 children
affected by KD, demonstrating higher HMGB1 values than
healthy controls. Furthermore, the highest values were detected
in early acute phase with a gradually decrement after deferves-
cence [55]. In addition, analyzing KD patients after intravenous
immunoglobulin treatment, Eguchi et al. demonstrated that poor-responder group was characterized by high HMGB1, representing a potential marker of therapy resistance [40]."

The abve found in this pdf.



There is so much I could post but some would be more specific to a sub type or co-morbid aspects bearing on the condition. Stepping back I feel I'm mostly done with my puzzle in the primary ways and a great deal of the detail. This piece is behind a pay wall, but is looking into the metabolic involvement in inflammation.

Beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses.

"Inflammasomes are protein complexes formed upon encounter of microbial or damage-associated stimuli. The main output of inflammasome assembly is activation of caspase-1, a protease involved in both pro-inflammatory and host-protective responses. Defined bacterial or viral ligands have been identified for the inflammasome-forming receptors AIM2, NLRP1, and NLRC4. The signals activating other inflammasomes, NLRP3, NLRP6, and pyrin, are less well understood. Recent studies implicated several low-molecular-weight compounds traditionally linked to metabolism, not immunity, in modulation of inflammasome signaling. Furthermore, genetic, pharmacological, or pathogen-mediated interference with energy metabolism also affects inflammasome activation. Here we review the findings on how microbial- and host-derived metabolites regulate activation of the NLRP3 and NLRP6 inflammasomes. We discuss the different models of how glycolysis and mitochondrial metabolism control the NLRP3 inflammasome. Finally, we summarize the findings on metabolic control of pyrin and point to open questions to be addressed to broaden our understanding of metabolism-inflammasome interactions."



Found this quite interesting as the cytokines mentioned are ones that keep surfacing with Autism and other brain related conditions involving the innate immune system. The second report ties THril gene mentioned related to Autism in the first report to Kawasaki disease as well.

Immunological cytokine profiling identifies TNF-α as a key molecule dysregulated in autistic children.


"Recent studies have suggested that the etiology of Autism Spectrum Disorder (ASD) may be caused by immunological factors, particularly abnormalities in the innate immune system. However, it is still unclear which specific cytokines may be of most importance. The current study therefore investigated which cytokines showed altered concentrations in blood in ASD compared with healthy control children and which were also correlated with symptom severity. Our study sample included 32 children diagnosed with ASD and 28 age and sex-matched typically developing children. Autism symptoms were measured using the Autistic Behavior Checklist (ABC) and blood samples were taken from all subjects. We used Milliplex cytokine kits to determine serum concentrations of 11 Th1, Th2 and Th17 related cytokines. Additionally, expression of THRIL (TNFα and hnRNPL related immunoregulatory LincRNA), a long non-coding RNA involved in the regulation of tumor necrosis factor- α (TNF-α), was determined using real-time PCR. Of the 11 cytokines measured only concentrations of TNF-α (p=0.002), IL-1β (p=0.02) and IL-17a (p=0.049) were significantly increased in ASD children compared to typically developing controls, but only TNF-α concentrations were positively correlated with severity of ASD symptoms on all 5 different ABC sub-scales and were predictive of an ASD phenotype (area under the curve = 0.74). Furthermore, THRIL RNA expression was significantly decreased in ASD children. Our results provide further support for altered innate immunity being an important autism pathogenic factor, with autistic children showing increased blood TNF-α concentrations associated with symptom severity, and decreased expression of the THRIL gene involved in regulating TNF-α."


The long noncoding RNA THRIL regulates TNFα expression through its interaction with hnRNPL.


"Thousands of large intergenic noncoding RNAs (lincRNAs) have been identified in the mammalian genome, many of which have important roles in regulating a variety of biological processes. Here, we used a custom microarray to identify lincRNAs associated with activation of the innate immune response. A panel of 159 lincRNAs was found to be differentially expressed following innate activation of THP1 macrophages. Among them, linc1992 was shown to be expressed in many human tissues and was required for induction of TNFα expression. Linc1992 bound specifically to heterogenous nuclear ribonucleoprotein L (hnRNPL) and formed a functional linc1992-hnRNPL complex that regulated transcription of the TNFα gene by binding to its promoter. Transcriptome analysis revealed that linc1992 was required for expression of many immune-response genes, including other cytokines and transcriptional and posttranscriptional regulators of TNFα expression, and that knockdown of linc1992 caused dysregulation of these genes during innate activation of THP1 macrophages. Therefore, we named linc1992 THRIL (TNFα and hnRNPL related immunoregulatory LincRNA). Finally, THRIL expression was correlated with the severity of symptoms in patients with Kawasaki disease, an acute inflammatory disease of childhood. Collectively, our data provide evidence that lincRNAs and their binding proteins can regulate TNFα expression and may play important roles in the innate immune response and inflammatory diseases in humans."



There is a lot to be gleaned from these two reports regarding a lot of Autism as there appears to be core relationships between the three conditions discussed and much Autism All throughout this thread I have alluded to studies about these three as they overlap with Autism biology dysfunction . Maybe I will post some of the things I see in the future. If you keep in my gene expression and the aspects of the cell types in the first report, esp. microglia, you might find it of interest. You can even understand the benefits of Metformin.

Cell specificity dictates similarities in gene expression in multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease


"Drug repurposing is an efficient approach in new treatment development since it leverages previous work from one disease to another. While multiple sclerosis (MS), Parkinson’s disease (PD), and Alzheimer’s disease (AD) are all neurodegenerative diseases of the central nervous system (CNS) and differ in many clinical and pathological aspects, it is possible that they may share some mechanistic features. We hypothesized that focusing on gene expression in a CNS cell type specific manner might uncover similarities between diseases that could be missed using whole tissue gene expression analyses. We found similarities and differences in gene expression in these three distinct diseases, depending upon cell type. Microglia genes were increased in all three diseases, and gene expression levels were correlated strongly among these three neurodegenerative diseases. In astrocytes and endothelia, upregulation and correlations were observed only between MS and PD, but not AD. Neuronal genes were down-regulated in all three diseases, but correlations of changes of individual genes between diseases were not strong. Oligodendrocyte showed gene expression changes that were not shared among the three diseases. Together these data suggest that treatments targeting microglia are most amenable to drug repurposing in MS, PD, and AD, while treatments targeting other CNS cells must be tailored to each disease."


Gene Expression from study

An integrative genomics approach identifies Hypoxia Inducible Factor-1 (HIF-1)-target genes that form the core response to hypoxia


"The transcription factor Hypoxia-inducible factor 1 (HIF-1) plays a central role in the transcriptional response to oxygen flux. To gain insight into the molecular pathways regulated by HIF-1, it is essential to identify the downstream-target genes. We report here a strategy to identify HIF-1-target genes based on an integrative genomic approach combining computational strategies and experimental validation. To identify HIF-1-target genes microarrays data sets were used to rank genes based on their differential response to hypoxia. The proximal promoters of these genes were then analyzed for the presence of conserved HIF-1-binding sites. Genes were scored and ranked based on their response to hypoxia and their HIF-binding site score. Using this strategy we recovered 41% of the previously confirmed HIF-1-target genes that responded to hypoxia in the microarrays and provide a catalogue of predicted HIF-1 targets. We present experimental validation for ANKRD37 as a novel HIF-1-target gene. Together these analyses demonstrate the potential to recover novel HIF-1-target genes and the discovery of mammalian-regulatory elements operative in the context of microarray data sets."



Supplementary Table s6 Files within file download
Particularly File013 and File014


I missed this excellent article and Visitor addendums when it was first published in 2015 and the only way I knew about it was the "Visitor" link in the sidebar comments.


Worth a read. Aluminum mainly. PDF



Saw this when it cam out, but it lends credence to barrier function issues in Autism.

Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders.



"Autism spectrum disorders (ASD) are complex conditions whose pathogenesis may be attributed to gene-environment interactions. There are no definitive mechanisms explaining how environmental triggers can lead to ASD although the involvement of inflammation and immunity has been suggested. Inappropriate antigen trafficking through an impaired intestinal barrier, followed by passage of these antigens or immune-activated complexes through a permissive blood-brain barrier (BBB), can be part of the chain of events leading to these disorders. Our goal was to investigate whether an altered BBB and gut permeability is part of the pathophysiology of ASD.


Postmortem cerebral cortex and cerebellum tissues from ASD, schizophrenia (SCZ), and healthy subjects (HC) and duodenal biopsies from ASD and HC were analyzed for gene and protein expression profiles. Tight junctions and other key molecules associated with the neurovascular unit integrity and function and neuroinflammation were investigated.


Claudin (CLDN)-5 and -12 were increased in the ASD cortex and cerebellum. CLDN-3, tricellulin, and MMP-9 were higher in the ASD cortex. IL-8, tPA, and IBA-1 were downregulated in SCZ cortex; IL-1b was increased in the SCZ cerebellum. Differences between SCZ and ASD were observed for most of the genes analyzed in both brain areas. CLDN-5 protein was increased in ASD cortex and cerebellum, while CLDN-12 appeared reduced in both ASD and SCZ cortexes. In the intestine, 75% of the ASD samples analyzed had reduced expression of barrier-forming TJ components (CLDN-1, OCLN, TRIC), whereas 66% had increased pore-forming CLDNs (CLDN-2, -10, -15) compared to controls.


In the ASD brain, there is an altered expression of genes associated with BBB integrity coupled with increased neuroinflammation and possibly impaired gut barrier integrity. While these findings seem to be specific for ASD, the possibility of more distinct SCZ subgroups should be explored with additional studies."


High Levels of Pro-Inflammatory Immune Cells in Intestines May Promote MS Activity, Study Reports

"People with multiple sclerosis have high levels of pro-inflammatory TH17 immune cells in their intestines that correlate with change in the micro-organism mix in their gut and the levels of their disease activity, a study reports.

Researchers said the findings suggest that diet, probiotics and therapies that regulate TH17 cells could help treat MS. Probiotics are supplements containing beneficial bacteria.

The study, “High frequency of intestinal TH17 cells correlates with microbiota alterations and disease activity in multiple sclerosis,” was published in the journal Science.

Research has shown that TH17 cells, also known as T helper 17 cells, play a role in the development of MS. In fact, they were the first harmful immune T-cells to infiltrate the central nervous system, according to studies in animals

Where TH17 cells become activated has been unclear, however. Studies in mice suggested it was mainly in the small intestine. Research has also indicated that their activation increases the potential for a person to develop an autoimmune brain disease like multiple sclerosis.

An autoimmune disease occurs when the immune system, which defends the body against disease, decides that a person’s healthy cells are foreign, and attacks those cells.

Researchers decided to see if the findings in mouse models of MS applied to people with the disease.

They discovered a link between higher levels of TH17 cells in MS patients’ intestines and autoimmune brain problems. They also found a correlation between higher levels of TH17 cells and changes in patients’ gut microbiome.

The team then identified which bacteria were changing in the gut.

Patients with increased levels of TH17 cells and higher disease activity had a higher ratio of Firmicutes to Bacteroidetes bacteria and more Streptococcus strains in their gut, particularly Streptococcus mitis and Streptococcus oralis. Previous studies have shown that these species promote TH17 cell differentiation in humans.

Cell differentiation involves a cell transforming from one cell type to another — usually a more specialized type. This dramatically changes a cell’s size, shape, metabolic — or fuel-burning — activity, and responsiveness to signals. Some studies have suggested a link between T-cell differentiation and brain autoimmune diseases.

“On the basis of our findings, we speculate that, under certain conditions, or because of still unknown virulence factors, these Streptococcus strains can colonize the small intestine and favor TH17 cell differentiation in the human gut mucosa [linings],” researchers wrote.

In addition to more Streptococcus bacteria, the team detected lower levels of Prevotella bacteria in MS patients with disease activity than in healthy controls or patients with no disease activity. This decrease may also promote TH17 cell differentiation because “Prevotella is capable of producing the anti-inflammatory metabolite propionate that limits intestinal TH17 cell expansion in mice,” the researchers wrote.

Overall, the team concluded that “our data demonstrate that brain autoimmunity is associated with specific microbiota modifications and excessive TH17 cell expansion in the human intestine.”

The findings suggest that regulating TH17 cell expansion, along with changes in diet aimed at regulating intestinal linings, could be ways to help treat MS."



This has some very good thoughts.

More Pieces To The Puzzle… Iron, Mercury, Sulfur, Fetal Hemoglobin, Heme Deficiency, Aluminum, Insulin, Gestational Diabetes, and B6



Some good pieces that show the connection of certain factors like sulfate and leaky gut issues. worthwhile though many probably know these basics. Mutations figure in too.
Nat2 and Sult function invoked here too.

Oxalates and MTHFR: Understanding the Gut-Kidney Axis




This anecdote is appropriate here I think:
From a board posting of a mother about her daughter.

"My daughter's results showed homozygous mutations in:




Which I'm guessing means to supplement with Vitamins B12 and D??? I don't really know what else to do. What kind of doctor could help look at this stuff or is it all up to us.... (as usual).....

"And the heterozygous mutations were in:

COMT v158M




MTR A2756G



CYP1A2 164A>C

Cyp2C9*3 A1075C

CYP2D6 S486T

CYP2D6 2850C>T


NAT2 I114T

NAT2 K268R

Any opinions greatly appreciated...."



Antigliadin Antibodies (AGA IgG) Are Related to Neurochemistry in Schizophrenia



The obligatory countenancing of scientists of the past having previously made assertions about certain biological connections to a certain medical issue is at times reasonable, but this first article uses this tact in saying the gut has long been associated by scientist with autism. Maybe so, but I shave followed this long enough to know that those that did were never taken seriously by the "establishment" of medicine and until fairly recently it was not taken seriously enough to investigate in mainstream medical institutions. Advocates of diet, probiotics, and other gut related supplements and nutrients were fighting an uphill battle. At least this may mean a corner is being turned, still why not say "some have proposed this and were usually dismissed."

Treating autism by targeting the gut

"Many of the papers reviewed support the idea of a gut-brain axis -- a way in which factors in the gut can affect processes in the brain. So these gastro-intestinal problems may have a more sinister side. The overgrowth of bad bacteria in the gut inevitably leads to an overproduction of by-products -- including toxins. These can make the gut lining more permeable. Then toxins, by-products and even undigested food can get into the bloodstream and travel to the brain....

However, the researchers found a significant body of evidence that reverting the gut microbiota to a healthy state can reduce ASD symptoms.

"Efforts to restore the gut microbiota to that of a healthy person has been shown to be really effective" continues Dr Li. "Our review looked at taking probiotics, prebiotics, changing the diet -- for example, to gluten- and casein-free diets, and faecal matter transplants. All had a positive impact on symptoms ."


and this with aspects of inflammation like much autism.

Inflammation in the Neurocircuitry of Obsessive-Compulsive Disorder


Mouse Study: Psychiatric Symptoms in Lupus Patients Tied to Inflammation



Trust any reading these will know their relevance. I just came across these studies, but they fit with all of things in this thread and agree with things I dealt with long ago. Sanity is overrated.

Low-grade endotoxemia in patients with severe autism {scroll down a bit for study}


Sex-related alterations of gut microbiota composition in the BTBR mouse model of autism spectrum disorder


Plasma Cytokine Profiles in Subjects with High-Functioning Autism Spectrum Disorders


Serum levels of vascular endothelial growth factor and its receptors in patients with severe autism


Alterations of circulating endogenous secretory RAGE and S100A9 levels indicating dysfunction of the AGE-RAGE axis in autism



Not totally futile. I am not myself on occasion.



I tried my best. It is futile.





Tuesday, May 23rd 2017 2PM 80°F 5PM 72°F 5-Day Forecast




Tuesday, May 23rd 2017 2PM 80°F 5PM 72°F 5-Day Forecast

Autism is linked to intelligence: People with 'smart genes' are more likely to have the disorder

Autism is linked to intelligence: People with 'smart genes' are more likely to have the disorder

I am heuristic, but this must be true.


Can anyone help me? See projection.

Autism is linked to intelligence: People with 'smart genes' are more likely to have the disorder


The Morning After by Maureen McGovern



Visitor: bringing new science into the public light always makes a difference, whether or not you ever personally witness the difference that it makes. Let me tell you how it makes a difference to me. My child had tics as an infant. It's THE main reason I slowed down and broke up school vaccinations for that child. Luckily, that symptom disappeared over time. Your information makes me very glad I was cautious at the time. I wish I had been even more cautious. Also, there is a friend I know well whose child has had tics since early childhood, still has them, but recently asked me about the meningitis vaccine, a shot I know less about but didn't it have a very small test subject group in southern south america somewhere, about as far away from standard US environmentally influenced kids as one could get. You know I will forward your information to my friend. It's about time other medical / neurological issues were examined in light of vaccine administration - and regularly discussed. It's especially important because it's easy to pawn off vaccine problems when the subject is a baby who can't talk - like those in the age range the doctor at UC David MIND limits himself to. The age range is much expanded in your reference - to children that may have been fine and dandy, until additional vaccinations. And they can TALK about it. You should repost this under Anne Dachel's post today.


Time to feed the beast.

II have found a lot since I last posted here, but doubt it makes any difference in posting all I discover. But, here is a new release on Pub Med. It talks about how the MMR has been clearly shown to have nothing to do with Autism and proceeds to test an association between vaccinations and other conditions excluding Autism. They find an association, or as they say "temporally related". They then say that because of the value of vaccines keep up the shots. Yet, they add "These findings warrant further investigation" but basically prove nothing. In the end signs point to yes, but yes is never an option.
Someone will surely pummel them over doing this study even though there is direct indictment of vaccines and any thinking reader would have to ask "is there a connection or not?".

Temporal Association of Certain Neuropsychiatric Disorders Following Vaccination of Children and Adolescents: A Pilot Case-Control Study.



"Although the association of the measles, mumps, and rubella vaccine with autism spectrum disorder has been convincingly disproven, the onset of certain brain-related autoimmune and inflammatory disorders has been found to be temporally associated with the antecedent administration of various vaccines. This study examines whether antecedent vaccinations are associated with increased incidence of obsessive-compulsive disorder (OCD), anorexia nervosa (AN), anxiety disorder, chronic tic disorder, attention deficit hyperactivity disorder, major depressive disorder, and bipolar disorder in a national sample of privately insured children.


Using claims data, we compared the prior year's occurrence of vaccinations in children and adolescents aged 6-15 years with the above neuropsychiatric disorders that were newly diagnosed between January 2002 and December 2007, as well as two control conditions, broken bones and open wounds. Subjects were matched with controls according to age, gender, geographical area, and seasonality. Conditional logistic regression models were used to determine the association of prior vaccinations with each condition.


Subjects with newly diagnosed AN were more likely than controls to have had any vaccination in the previous 3 months [hazard ratio (HR) 1.80, 95% confidence interval 1.21-2.68]. Influenza vaccinations during the prior 3, 6, and 12 months were also associated with incident diagnoses of AN, OCD, and an anxiety disorder. Several other associations were also significant with HRs greater than 1.40 (hepatitis A with OCD and AN; hepatitis B with AN; and meningitis with AN and chronic tic disorder).


This pilot epidemiologic analysis implies that the onset of some neuropsychiatric disorders may be temporally related to prior vaccinations in a subset of individuals. These findings warrant further investigation, but do not prove a causal role of antecedent infections or vaccinations in the pathoetiology of these conditions. Given the modest magnitude of these findings in contrast to the clear public health benefits of the timely administration of vaccines in preventing mortality and morbidity in childhood infectious diseases, we encourage families to maintain vaccination schedules according to CDC guidelines."


anorexia nervosa; anxiety disorder; influenza; meningococcus; obsessive–compulsive disorder; tic disorder; vaccination



I messed the order of the last post up. Here is how it should be ordered.

This is another that is preliminary, but seems accurate. They think the treatment targets the NLRP3 pathway which is one of the areas I have found relevant, at least in our case. NLRP3 or NALP3 laced through this thread.

Pill for Menstrual Pain Restores Memory in Mice with Alzheimer's

"A surprising discovery has been made in the treatment of Alzheimer's disease. An anti-inflammatory drug used to treat menstrual pain completely reversed memory symptoms in mice with Alzheimer's.

The drug, called mefenamic acid, is a so-called non-steroidal anti-inflammatory drug, or NSAID, used to relieve menstrual cramps.

In experiments with mice specially bred to have Alzheimer's symptoms, the rodents predictably developed memory problems over time.

Ten of the Alzheimer's mice were treated for one month with mefenamic acid that was contained in tiny pumps implanted under their skin. Ten other mice with memory difficulties were injected with pumps of a placebo, or inactive substance.

The rodents were placed in maze to train them to get around the obstacles.

In a Skype interview, Mike Daniels, who participated in the research at the University of Manchester in Britain, said "We tried to train the mice once they had Alzheimer's disease. The Alzheimer's mice are untrainable. They cannot learn that maze."

"But the results in the treated mice were stunning."

"What was just amazing is that this drug seemed to render the mice completely normal,” Daniels said. “It's something we haven't really seen before, but there needs to be a lot more work done to really confirm whether this is real.”

Targeting inflammation

"The findings were published in the journal Nature Communications. The research was led by David Brough of the University of Manchester."

Daniels said brain-imaging shows a lot of harmful inflammation in the brains of Alzheimer's patients.

"Researchers believe mefenamic acid targets an inflammatory pathway called NLRP3, reducing inflammation."

"Scientist found that no other NSAIDS — including ibuprofen, which is commonly taken for pain — reduced the brain inflammation."

"Whether it works in patients at all stages of Alzheimer's — from people with mild cognitive impairment to those who are severely affected — is difficult to say, according to co-author Jack Rivers-Auty."

"Maybe, if this was translated into the clinic, we would definitely want to put it into people at the early stages of the disease to try to slow the progress or stop the progress of the disease," said Rivers-Auty, "rather than taking the ambitious aim of taking someone who fully has Alzheimer's disease, has all the symptoms — incredible memory loss, incredible cognitive impairment — and trying to reverse those symptoms. That might be very difficult."


Multiple inflammasome complexes are activated in autistic spectrum disorders.


"Inflammasomes are multimeric protein platforms involved in the regulation of inflammatory responses whose activity results in the production of proinflammatory cytokines. Because neuroinflammation is observed in autistic spectrum disorders (ASD), a neurologic condition of childhood resulting in a complex behavioural impairment, we analyzed the inflammasomes activity in ASD. Additionally we verified whether alterations of the gastrointestinal (GI) barriers might play a role in inflammasomes activation.


The activity of the inflammasomes, the concentration of the inflammasomes-derived proinflammatory cytokines interleukin (IL)-1β and IL-18, and serum parameters of GI damage were analyzed in 25 ASD children, 23 healthy siblings (HS) and 30 unrelated age-matched healthy controls (HC).


A significant upregulation of the AIM2 and the NLRP3 inflammasomes and an increased production of IL-1β and IL-18 that was associated with a consistent reduction of IL-33, an anti inflammation cytokine were observed in ASD alone. Notably, in a possible immune-mediated attempt to dampen inflammation, IL-37, a suppressor of innate inflammatory responses, was significantly augmented in these same children. Finally, intestinal fatty acid binding protein (IFABP), an index of altered GI permeability, was significantly increased in serum of ASD and HS.


These results show that the inflammasomes are activated in ASD and shed light on the molecular mechanisms responsible for ASD-associated neuroinflammation. The observation that GI alterations could be present as well in ASD offers a possible link between such alterations and neuroinflammation. Therapeutic strategies targeting inflammasome activation could be useful in ASD."



This is another that is preliminary, but seems accurate. They think the treatment targets the NLRP3 pathway which is one of the areas I have found relevant, at least in our case. NLRP3 or NALP3 laced through this thread.

Pill for Menstrual Pain Restores Memory in Mice with Alzheimer's

"A surprising discovery has been made in the treatment of Alzheimer's disease. An anti-inflammatory drug used to treat menstrual pain completely reversed memory symptoms in mice with Alzheimer's.

The drug, called mefenamic acid, is a so-called non-steroidal anti-inflammatory drug, or NSAID, used to relieve menstrual cramps.

In experiments with mice specially bred to have Alzheimer's symptoms, the rodents predictably developed memory problems over time.

Ten of the Alzheimer's mice were treated for one month with mefenamic acid that was contained in tiny pumps implanted under their skin. Ten other mice with memory difficulties were injected with pumps of a placebo, or inactive substance.

The rodents were placed in maze to train them to get around the obstacles.

In a Skype interview, Mike Daniels, who participated in the research at the University of Manchester in Britain, said "We tried to train the mice once they had Alzheimer's disease. The Alzheimer's mice are untrainable. They cannot learn that maze."

"But the results in the treated mice were stunning."

"What was just amazing is that this drug seemed to render the mice completely normal,” Daniels said. “It's something we haven't really seen before, but there needs to be a lot more work done to really confirm whether this is real.”


Multiple inflammasome complexes are activated in autistic spectrum disorders.


"Inflammasomes are multimeric protein platforms involved in the regulation of inflammatory responses whose activity results in the production of proinflammatory cytokines. Because neuroinflammation is observed in autistic spectrum disorders (ASD), a neurologic condition of childhood resulting in a complex behavioural impairment, we analyzed the inflammasomes activity in ASD. Additionally we verified whether alterations of the gastrointestinal (GI) barriers might play a role in inflammasomes activation.


The activity of the inflammasomes, the concentration of the inflammasomes-derived proinflammatory cytokines interleukin (IL)-1β and IL-18, and serum parameters of GI damage were analyzed in 25 ASD children, 23 healthy siblings (HS) and 30 unrelated age-matched healthy controls (HC).


A significant upregulation of the AIM2 and the NLRP3 inflammasomes and an increased production of IL-1β and IL-18 that was associated with a consistent reduction of IL-33, an anti inflammation cytokine were observed in ASD alone. Notably, in a possible immune-mediated attempt to dampen inflammation, IL-37, a suppressor of innate inflammatory responses, was significantly augmented in these same children. Finally, intestinal fatty acid binding protein (IFABP), an index of altered GI permeability, was significantly increased in serum of ASD and HS.


These results show that the inflammasomes are activated in ASD and shed light on the molecular mechanisms responsible for ASD-associated neuroinflammation. The observation that GI alterations could be present as well in ASD offers a possible link between such alterations and neuroinflammation. Therapeutic strategies targeting inflammasome activation could be useful in ASD."

Targeting inflammation

"The findings were published in the journal Nature Communications. The research was led by David Brough of the University of Manchester."

Daniels said brain-imaging shows a lot of harmful inflammation in the brains of Alzheimer's patients.

"Researchers believe mefenamic acid targets an inflammatory pathway called NLRP3, reducing inflammation."

"Scientist found that no other NSAIDS — including ibuprofen, which is commonly taken for pain — reduced the brain inflammation."

"Whether it works in patients at all stages of Alzheimer's — from people with mild cognitive impairment to those who are severely affected — is difficult to say, according to co-author Jack Rivers-Auty."

"Maybe, if this was translated into the clinic, we would definitely want to put it into people at the early stages of the disease to try to slow the progress or stop the progress of the disease," said Rivers-Auty, "rather than taking the ambitious aim of taking someone who fully has Alzheimer's disease, has all the symptoms — incredible memory loss, incredible cognitive impairment — and trying to reverse those symptoms. That might be very difficult."



Some would say this requires more confirmation, other studies would align with this report. My own experience says it is legitimate.

Wheat can cause immune response in people without Celiac disease, study says

'People with a wheat sensitivity, but not celiac's disease or a wheat allergy, are not imagining symptoms they feel after eating wheat, according to a new study.

Researchers at Columbia University Medical Center report people without celiac's disease can experience a body-wide immune response to wheat thought to be related to intestinal cell damage and a weakening of the intestinal barrier, which may suggest a method of identifying and treating the condition.

Celiac disease is a genetic autoimmune disorder causing an immune response to gluten -- found in wheat, barley and rye -- attacking the lining of the small intestine, causing abdominal pain, diarrhea and bloating.

With growing awareness of celiac disease in recent years, the popularity of a gluten-free diet has also grown. Researchers in other studies have suggested a gluten-free diet is unhealthy in the absence of a condition like celiac.

The new study suggests non-celiac gluten or wheat sensitivity, or NCWS, can be identified in patients based on system-wide inflammation caused by the grains.

"These results shift the paradigm in our recognition and understanding of non-celiac wheat sensitivity and will likely have important implications for diagnosis and treatment," Dr. Umberto Volta, a professor of internal medicine at the University of Bologna, said in a press release. "Considering the large number of people affected by the condition and its significant negative health impact on patients, this is an important area of research that deserves much more attention and funding."

For the study, published in the journal BMJ Gut, researchers examined 80 people with NCWS, 40 with celiac disease and 40 who were healthy.

While both celiac and NCWS patients showed damage to their small intestines similar to celiac disease, NCWS patients showed signs of innate systemic immune activation. The researchers say this indicates a completely different response to wheat or gluten they link to intestinal cell damage and weakening of the intestinal barrier.

Patients in the study with NCWS who consumed a gluten-free diet for six months saw their immune systems calm down and reported symptoms subsided the longer they stayed on the diet.

"Our study shows that the symptoms reported by individuals with this condition are not imagined, as some people have suggested," said Dr. Peter Green, director of the Celiac Disease Center at Columbia University. "It demonstrates that there is a biological basis for these symptoms in a significant number of these patients."


If I could bold some of the words I would have bolded these:
"system-wide inflammation caused by the grains"
"NCWS patients showed signs of innate systemic immune activation."
"Patients in the study with NCWS who consumed a gluten-free diet for six months saw their immune systems calm down and reported symptoms subsided the longer they stayed on the diet."


Does the Immune System Have a Role in Battling Autism?



Hi Grace, you are welcome. How vaccines tie to interferon-γ, also labeled Interferon Gamma, is of interest. A number of posts in this thread address aspects of interferon-γ as it may pertain to Autism. I think the article goes a bit far suggesting we may simply be a platform for immune/pathogen evolution, but there does appear to be a strong symbiosis and a early and/or strong continuous dysfunction in this and other immune related function with pathogens could alter neurological function and development.

Another report just released addressing the same information adds more possible light.

Does the Immune System Have a Role in Battling Autism?

"Replenishing the spinal fluid of the mice with interferon gamma is enough to restore social behavior in the mice. Diazepam, a sedative that boosts the activity of inhibitory neurons, has the same effect."...

"If the immune system evolved alongside social behavior, this might explain the results of other autism studies. A study published earlier this year, for example, suggests that some pregnant women who go on to have children with autism and intellectual disability have elevated blood levels of interferon gamma."

"This result may seem at odds with the finding that interferon gamma is needed for social behavior, but too much of the molecule might shut off its activity."

"The role of immune molecules in the brain is likely to be a delicate balance, with specific levels needed at specific times, says Pardo-Villamizar. “The immune system during brain development works like an orchestra,” he says.

"The findings may explain the observation that some children with autism seem to become more sociable when they have a fever, Kipnis says. Elevated levels of molecules such as interferon gamma accompany fevers."

"Kipnis says understanding the immune link to social behavior might help scientists find drugs that treat autism. Clinicians might be able to administer the treatment in the cerebrospinal fluid, he says, rather than via the brain."


A few years back in this thread I had posted this:

"Autism: An Overview"

Written and Maintained by Lewis Mehl-Madrona, M.D., Ph.D.

"Gamma Interferon Theory

Dr. Vijendra Singh has found elevated levels of interleukin-12 and gamma interferon in autistic patients. Opioids can increase levels of gamma interferon."

The rest of that post also spoke of how NK cells and T-Lymphocytes. The quote acutally is:
"Sulfation problems have been described by Rosemary Waring at the University of Birmingham in autism which could lead to an inability to handle virus infections, with a disruption of cell-mediated immunity® as well as an impairment of natural killer cell function.® Unlike the situation with type I interferons, which are released by infected cells, interferon gamma (a type II interferon) is released by T lymphocytes and natural killer cells, but that happens not when they themselves have been activated, but rather, when they are alerted to the presence of infection by other immune cells or by a superantigen or a chemical mitogen."

So, while it appears to be that interferon Gamma is a player in some amount of autism weather it is too much or too little or even a vacillating amount that is the problem is still something I have not found an answer.

The link to the latter in I quoted can be found under the heading:
Gamma Interferon Theory at the link below
http://www.healing-arts.org/children/autism-overview.htm#Gamma Interferon

Grace Green

Thank you, Visitor, for posting this find. This sounds to me very much like "Vaccines cause Autism (M.E./Alzheimers etc.). I look forward to hearing how this progresses.


This report postulates the general ideas of effects of the immune system/pathogen interaction and brain function and social behavior. It alludes to involving Autism though our case was extreme with a reactive social condition , one without autonomy.

Shocking New Role Found for the Immune System: Controlling Social Interactions

"In a startling discovery that raises fundamental questions about human behavior, researchers at the University of Virginia School of Medicine have determined that the immune system directly affects – and even controls – creatures’ social behavior, such as their desire to interact with others.

So could immune system problems contribute to an inability to have normal social interactions? The answer appears to be yes, and that finding could have significant implications for neurological diseases such as autism-spectrum disorders and schizophrenia.

“The brain and the adaptive immune system were thought to be isolated from each other, and any immune activity in the brain was perceived as sign of a pathology. And now, not only are we showing that they are closely interacting, but some of our behavior traits might have evolved because of our immune response to pathogens,” explained Jonathan Kipnis, Ph.D., chairman of UVA’s Department of Neuroscience. “It’s crazy, but maybe we are just multicellular battlefields for two ancient forces: pathogens and the immune system. Part of our personality may actually be dictated by the immune system.”...

"It was only last year that Kipnis, the director of UVA’s Center for Brain Immunology and Glia, and his team discovered that meningeal vessels directly link the brain with the lymphatic system. That overturned decades of textbook teaching that the brain was “immune privileged,” lacking a direct connection to the immune system. The discovery opened the door for entirely new ways of thinking about how the brain and the immune system interact."

"The follow-up finding is equally illuminating, shedding light on both the workings of the brain and on evolution itself. The relationship between people and pathogens, the researchers suggest, could have directly affected the development of our social behavior, allowing us to engage in the social interactions necessary for the survival of the species while developing ways for our immune systems to protect us from the diseases that accompany those interactions. Social behavior is, of course, in the interest of pathogens, as it allows them to spread."

"The UVA researchers have shown that a specific immune molecule, interferon gamma, seems to be critical for social behavior and that a variety of creatures, such as flies, zebrafish, mice and rats, activate interferon gamma responses when they are social. Normally, this molecule is produced by the immune system in response to bacteria, viruses or parasites. Blocking the molecule in mice using genetic modification made regions of the brain hyperactive, causing the mice to become less social. Restoring the molecule restored the brain connectivity and behavior to normal. In a paper outlining their findings, the researchers note the immune molecule plays a “profound role in maintaining proper social function.”...

"The researchers note that a malfunctioning immune system may be responsible for “social deficits in numerous neurological and psychiatric disorders.” But exactly what this might mean for autism and other specific conditions requires further investigation. It is unlikely that any one molecule will be responsible for disease or the key to a cure. The researchers believe that the causes are likely to be much more complex. But the discovery that the immune system – and possibly germs, by extension – can control our interactions raises many exciting avenues for scientists to explore, both in terms of battling neurological disorders and understanding human behavior."...

Kipnis and his team worked closely with UVA’s Department of Pharmacology and with Vladimir Litvak’s group, Ph.D., at the University of Massachusetts Medical School. Litvak’s team developed a computational approach to investigate the complex dialogue between immune signaling and brain function in health and disease.

“Using this approach we predicted a role for interferon gamma, an important cytokine secreted by T lymphocytes, in promoting social brain functions,” Litvak said. “Our findings contribute to a deeper understanding of social dysfunction in neurological disorders, such as autism and schizophrenia, and may open new avenues for therapeutic approaches.”



Yeah Benedetta,

It has been 20 years for me on these particular matters. It is a bit vindicating to see the gut microbiome being tied to CFS now and leaky gut given validity. Yet, those I tried to explain this to then along with all the other aspects. have long dismissed what I said or say. At least wee know and people can be helped.


Thanks Nick for the last two up dates. I don't give zinc, but all the rest - I do.

Interesting about the gut microbes. Finally; after years and year and years -- leaky gut is now in pub med - nih research papers; and no one is making fun of them now. Yeah - now - 20 years later. Geesh.


Chronic fatigue syndrome is in your gut, not your head

"Our work demonstrates that the gut bacterial microbiome in chronic fatigue syndrome patients isn't normal, perhaps leading to gastrointestinal and inflammatory symptoms in victims of the disease," said Maureen Hanson, the Liberty Hyde Bailey Professor in the Department of Molecular Biology and Genetics at Cornell and the paper's senior author. "Furthermore, our detection of a biological abnormality provides further evidence against the ridiculous concept that the disease is psychological in origin."...

"At the same time, the researchers discovered specific markers of inflammation in the blood, likely due to a leaky gut from intestinal problems that allow bacteria to enter the blood, Giloteaux said.

Bacteria in the blood will trigger an immune response, which could worsen symptoms.

The researchers have no evidence to distinguish whether the altered gut microbiome is a cause or a whether it is a consequence of disease, Giloteaux added.

In the future, the research team will look for evidence of viruses and fungi in the gut, to see whether one of these or an association of these along with bacteria may be causing or contributing to the illness."



Hi Benedetta, good to hear from you.

There are a number of things happening and contributing to the whole of the system dysfunction. I have mentioned aldehydes and alcohol/ethanol related genes in the past and Candida's contribution with aldehydes. This next report is long , but very good and it speaks of endogenous and exogenous aldehydes as they may pertain to autism. Getting the yeast under control was very helpful in our case.

The Pivotal Role of Aldehyde Toxicity in Autism Spectrum Disorder: The Therapeutic Potential of Micronutrient Supplementation

Aldehydes generated by gut microbiota
"Gastrointestinal abnormalities are common among those suffering from neurodevelopmental disorders, including ASD. In addition to malabsorption problems in unhealthy intestines, abnormal microbiota of the gut appear to be contributing factors in ASD mouse models28 as well as in humans.29 One suggested explanation is that yeast and bacterial gut flora generate toxins, including alcohols and aldehydes, such as methylg-lyoxal,30 during the metabolism of various carbohydrates. Methylglyoxal is a potent aldehyde implicated in numerous disorders.3 Certainly, Candida infections common in ASD31 have long been suspected of converting carbohydrates into ethanol,32 which is subsequently metabolized to the potent neurotoxin, acetaldehyde. Alterations in the normal gut microflora of mice have also been linked to oxidative stress.33 Research into the microbiota–gut–brain axis in neurodevelopmental disorders is in its earliest stages, but aldehydes may play an important role."...

"Taken together, aldehyde toxicity induces micronutrient deficiencies in sulfur-containing antioxidants, Zn2+, B6, B1, Mg2+, and folate, creating oxidative stress and disruptions in a cascade of metabolic reactions."



You have hit on a lot of great things - almost information overload since I got behind. Sorry.

Vasculitiis of the peripheral small capillaries was a good one article.

You hit upon Parkinson disease along those same lines. I am worried about just that for my son. I am worried about early on set Parkinson. My Father has it, and my son tends toward constipation.

I am making Kimchi right now. I raised the prettiest Nappa cabbage this spring. They have a curly leaf and look like a big green flower. I need to watch his diet a lot more. He is gluten free and casein free, but I am not getting those probiotics and fiber down him like I should. Or vitamins.

In spite of the article that said too many vitamins might be the problem - I would dare say it is the opposite - the gut is not absorbing . But as Jenny says - is that the right kind of vitamin - Folic or folate.

Toxins - metals has an extra electron on the out ring and wants to travel in pairs - was a great article. That is why everything like aluminum and antimony comes out first before mercury. That kind of ties it all together when it comes to the gold salts. Does gold bind with these heavy metals -- the answer is yes. Once attached to gold does it make it easier for the body to get rid of both gold and the heavy metal. I bet it does.

Raynards -- right on-- my neighbor's grand daughter in middle school has Raynards . She is thinking on things - I have pointed out to her that Raynards is a form of vasculiitis just like Kawaskis is.

Lots and lots of great stuff.

Thank You Nick.


Oh, I have missed a lot!

Let me catch up on it all this reading.

You are my friend too Nick and Thus, I love you too.


Where is love. I started this journey based on pure love. I implore those of you supremely educated in love to think in kind.

nick63 @twc.com

Benedetta. I ,love you and wonder at your insight at once. God bless you.


You are wrong. It is a form of autism I am describing. Cord clamping causes, or contributes, to very little autism.


Hope to develop this.

Measles and Nectins...so far Nectin 4 in epithelial cells. This would relate to lower cancer rates in Autism and the microvascular/capillary issues with the angiogenesis recently reported on in some with Autism. Possible Polio virus and flu vaccine ties. It is interesting certain measles virus vaccines are being worked on for certain cancers.


I still don't know if boosted Vitamin D could kink in GC-MAF, though I lean against the idea. What is somewhat convincing is the relationship of the GC protein with other elements perturbed in immune/cell/clock circadian ryhtm function with Autism.


I don't know why the GC protein is not available yet, but Dr. Bradstreet was correct. Is it just Nagalase levels hindering DBP? Whether that is the main issue in D3 not being transported to the receptor what I have used< Olmesartan, accomplishes the task it appears by also being able to activate the VDR. Therefore GC-Maf and Olmesartan would accomplish the same thing.


In the GC Gene card info one of the drugs for the GC gene is acetaminophen..hmmm. The GC gene biological processes also effected are:

female pregnancy IEA
lactation IEA
steroid metabolic process TAS
response to nutrient levels IEA
response to estradiol




Association of polymorphisms in the vitamin D receptor gene and serum 25-hydroxyvitamin D levels in children with autism spectrum disorder.


"Vitamin D is implicated in several aspects of human physiology, and polymorphisms in the vitamin D receptor gene (VDR) are associated with a variety of neuropsychiatric disorders. The aims of this study are to determine whether VDR polymorphisms are associated with autism spectrum disorder (ASD), to examine serum 25-hydroxyvitamin D (25(OH)D) levels in ASD, and to explore whether VDR polymorphisms influence serum 25(OH)D levels. We investigated 480 subjects (237 children with ASD and 243 healthy controls) for the following VDR polymorphisms: TaqI, BsmI, FokI, ApaI, and Cdx2.Within the same samples, 25(OH)D levels were available only for 85 patients and 82 controls. The Cdx-2 variation was shown to deviate from Hardy-Weinberg equilibrium in the controls and was therefore excluded from the study. We found that the frequency of rare FokI TT, TaqI CC, and BsmI AA genotypes differed significantly between children with ASD and the controls (p=0.042, p=0.016, p=0.038, respectively). After correction for multiple testing, only the TaqI CC genotype remained significant. Further analysis using a recessive model showed that rare genotypes of these polymorphisms were significantly higher in patients compared to controls (p=0.045, p=0.005 and p=0.031, respectively). However, no significant association was found between ApaI and ASD. We found serum 25(OH)D levels to be significantly higher in children with ASD (p<0.001) and that the FokI polymorphism had an effect on serum 25(OH)D levels in children with ASD (p=0.041). Additionally, we found the haplotype GTTT (BsmI/TaqI/FokI/ApaI) conferred an increased risk for developing ASD (p=0.022; odds ratio [95% confidence interval]=2.322 [1.105-4.879]). This is the first clinical study evaluating the association between serum 25(OH)D levels and VDR polymorphisms in children with ASD. Our results demonstrated a significant association between TaqI, BsmI, and FokI polymorphisms and ASD and showed for the first time that FokI polymorphisms and haplotype GTTT (BsmI/TaqI/FokI/ApaI) are associated with an increased risk of ASD. Our findings support the hypothesis that 25(OH)D is involved in the pathophysiology of autism and that serum 25(OH)D levels may be affected by FokI polymorphisms in children with ASD. Our results should be considered as preliminary and needs confirmation by future studies."




If I am wrong in the case of other groups with Autism it also may be the gene expression of the VDR is reduced and Vitamin D may levels rise, but not active the VDR. In such a scenario it might be possible that very high D levels could activate the fewer vitamin D receptors.


I had taken a break from all of this and have not considered the possible effect of very high D3 as resolving some of the problem, at least in some cases. In general I have found I am not in the main on Vitamin D supplementation and we do not use it. My wife tested very high in D3 and low in D2 and that was without supplementation. The sulfated vitamin D being required as well as LDL levels might be part of the problem. It also seems pathogen associated inflammation and sterile inflammation aspect may be occurring for many at the same time and this complicates the matter. The blood irradiation might reduce pathogens that provoke inflammation. But, the bigger problem is how the immune system is working and blood irradiation in Autism would likely produce mild benefits for a very brief time.

I don't think the issue is very simple though. Where there is immune dysfunction ate multiple levels, or individuals with additional biological variants, those effecting the gut vs those effecting the vascular or other area D levels and interaction may be more or less pathological and could benefit some areas while hindering others.

This report reflects my feelings about Vitamin D and feel it is probably more often how Vitamin D relates to Autism then viewing it as a long term treatment.

Infant Exposure to Excessive Vitamin D: A Risk Factor for Autism


A variant in some could complicate the issue of whether Vitamin D could be somewhat helpful.

Low Vitamin-D Levels Combined with PKP3-SIGIRR-TMEM16J Host Variants Is Associated with Tuberculosis and Death in HIV-Infected and -Exposed Infants



Interesting posts recently, Visitor!

It's my understanding that gluten has been used in labs to induce vitamin D deficiency. I can see that tying in in certain ways. Is vitamin D's situation in autism similar to what's been found out about thyroid stuff of late, that just because there are circulating blood levels doesn't necessarily mean its being used, or used correctly, taken up by cells/tissues, etc. Because there are other case reports of spontaneous correction of autistic symptoms upon use of clinically higher vitamin D3 levels - whether by accident or on purpose. Might it kick in GcMaf at a certain threshold, or mitigate mis? Am I interpreting this correctly?

How about this? Can any of this be tied together?


Since the angiogenesis in brain vessels in Autism is not verified, though I currently think it is involved in some or many, this association is speculative. I don't know if a lack of GCMAF is a factor in possible angiogenesis in the brain, yet this report seems noteworthy. There is not a lot to go on in this area so far. How GCMAF and MIF interact is of interest.

Effects of vitamin D(3)-binding protein-derived macrophage activating factor (GcMAF) on angiogenesis.


"BACKGROUND: The vitamin D(3)-binding protein (Gc protein)-derived macrophage activating factor (GcMAF) activates tumoricidal macrophages against a variety of cancers indiscriminately. We investigated whether GcMAF also acts as an antiangiogenic factor on endothelial cells.


The effects of GcMAF on angiogenic growth factor-induced cell proliferation, chemotaxis, and tube formation were examined in vitro by using cultured endothelial cells (murine IBE cells, porcine PAE cells, and human umbilical vein endothelial cells [HUVECs]) and in vivo by using a mouse cornea micropocket assay. Blocking monoclonal antibodies to CD36, a receptor for the antiangiogenic factor thrombospondin-1, which is also a possible receptor for GcMAF, were used to investigate the mechanism of GcMAF action.


GcMAF inhibited the endothelial cell proliferation, chemotaxis, and tube formation that were all stimulated by fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor-A, or angiopoietin 2. FGF-2-induced neovascularization in murine cornea was also inhibited by GcMAF. Monoclonal antibodies against murine and human CD36 receptor blocked the antiangiogenic action of GcMAF on the angiogenic factor stimulation of endothelial cell chemotaxis.


In addition to its ability to activate tumoricidal macrophages, GcMAF has direct antiangiogenic effects on endothelial cells independent of tissue origin. The antiangiogenic effects of GcMAF may be mediated through the CD36 receptor."


As far as taking Vitamin d{at least D3} this may be good to note.

"Children with autism often have very high levels of vitamin D3, occasionally toxic levels (and low levels of D2) which may be produced by gut bacteria. We do not recommend administering vitamin D3, which may result in severe hyperactivity, unless the child has had a vitamin D level test."


Macrophage migration inhibitory factor (MIF or MMIF)

"A cytokine recently linked to autism is macrophage migration inhibitory factor (MIF). MIF is a pro-inflammatory immune regulator that is constitutively expressed in brain tissues, and has important influences on neural and endocrine systems. This macrophage migration inhibitory factor cytokine is produced by neuroendocrine and immune tissues. Macrophage migration inhibitory factor possesses glucocorticoid-antagonist properties within the immune system and participates in the regulation of several endocrine circuits.
•Plasma levels of macrophage migration inhibitory factor (MIF) were higher in individuals with autism.
•Individuals with autism with the highest levels of plasma MIF were found to have the most severe behavioral symptoms.
•Macrophage migration inhibitory factor is of critical importance for the host response to microbial infections and in several autoimmune diseases.
•Macrophage migration inhibitory factor expression is usually constitutive at low levels."



While one may or may not have Kawasaki's there is an aspect that can be autoimmune based and as put forward earlier in this thread and may be related to mercury though other pathogens can be the trigger. This, again, associates HMGB1 with a vascular condition though MIF levels in Kawasaki's and those with only Autism show differing values. I can not speculate what the presence of both conditions together would give in MIF levels, but their is a partially shared pathology it appears.

New understanding of autoimmune diseases

"Thanks to a recent Yale study, physicians may soon adopt a new method to combat rheumatoid arthritis and other autoimmune diseases."

"Researchers at the Yale School of Medicine have discovered a transcription factor, ICBP90, that has been shown to regulate the expression levels of MIF — a gene that has been implicated in a number of diseases, primarily autoimmune diseases and cancer. The transcription factor, a protein responsible for facilitating the production of RNA from DNA, binds to MIF’s promoter region, which helps to regulate and initiate transcription. According to the study authors, by identifying the connection between ICBP90 and MIF, researchers can develop new methods of drug treatment for diseases including rheumatoid arthritis and cancer by targeting the gene in a more precise and personalized way."...

"Low expression of MIF has been shown to have benefits against certain diseases. Bucala noted that low expression of MIF confers resistance to death from malaria. Low expression also decreases susceptibility to autoimmune diseases and lessens their severity."...

"There are two potential therapeutic implications of the study, according to Maor Sauler, study co-author and medical school professor. The first will allow researchers to better understand how MIF is involved in disease, particularly in differentiating what is caused by environmental stimuli, and what is caused by the gene. The second implication is that scientists will be able to identify the MIF polymorphism in individual patients. This will help to indicate patients’ susceptibility to autoimmune diseases as well as signal which patients will respond best to anti-MIF or anti-ICBP90 therapy, Sauler added."


High mobility group box 1 (HMGB1) and macrophage migration inhibitory factor (MIF) in Kawasaki disease.



"To investigate whether two proinflammatory cytokines, high mobility group box 1 (HMGB1) and macrophage migration inhibitory factor (MIF) are involved in the development of Kawasaki disease (KD).


Twenty-seven patients with KD were included in this study. Eleven patients with sepsis and 28 healthy children served as controls. Serum levels of HMGB1 and MIF were measured by corresponding enzyme-linked immunosorbent assay (ELISA) kits, respectively. Real-time polymerase chain reaction (PCR) was used to quantify the expression levels of genes encoding receptor for advanced glycation end-products (RAGE), an HMGB1 receptor, and CD74, an MIF receptor in peripheral blood mononuclear cells (PBMCs).


Serum levels of HMGB1 and MIF in KD patients were the highest in the early acute phase and gradually decreased after defervescence. Serum HMGB1 and MIF levels in KD patients were significantly higher than those in controls (HMGB1, p<0.001; MIF, p<0.01). The expression levels of the RAGE gene and CD74 gene in KD patients were significantly higher than those in controls (RAGE, p<0.001; CD74, p<0.01).


These data suggest that HMGB1 and MIF play an important role in immune responses in KD patients."


Macrophage migration inhibitory factor and autism spectrum disorders.



"Autistic spectrum disorders are childhood neurodevelopmental disorders characterized by social and communicative impairment and repetitive and stereotypical behavior. Macrophage migration inhibitory factor (MIF) is an upstream regulator of innate immunity that promotes monocyte/macrophage-activation responses by increasing the expression of Toll-like receptors and inhibiting activation-induced apoptosis. On the basis of results of previous genetic linkage studies and reported altered innate immune response in autism spectrum disorder, we hypothesized that MIF could represent a candidate gene for autism spectrum disorder or its diagnostic components.


Genetic association between autism spectrum disorder and MIF was investigated in 2 independent sets of families of probands with autism spectrum disorder, from the United States (527 participants from 152 families) and Holland (532 participants from 183 families). Probands and their siblings, when available, were evaluated with clinical instruments used for autism spectrum disorder diagnoses. Genotyping was performed for 2 polymorphisms in the promoter region of the MIF gene in both samples sequentially. In addition, MIF plasma analyses were conducted in a subset of Dutch patients from whom plasma was available.


There were genetic associations between known functional polymorphisms in the promoter for MIF and autism spectrum disorder-related behaviors. Also, probands with autism spectrum disorder exhibited higher circulating MIF levels than did their unaffected siblings, and plasma MIF concentrations correlated with the severity of multiple autism spectrum disorder symptoms.


These results identify MIF as a possible susceptibility gene for autism spectrum disorder. Additional research is warranted on the precise relationship between MIF and the behavioral components of autism spectrum disorder, the mechanism by which MIF contributes to autism spectrum disorder pathogenesis, and the clinical use of MIF genotyping."


Serum levels of macrophage migration inhibitory factor in children and adolescents with autistic disorders


"Background: There is growing awareness of an immunological involvement in children with autistic disorder (AD). Studies suggest that innate rather than adaptive neuroimmune responses are associated with autism. Macrophage migration inhibitory factor (MIF), being an upstream regulator of innate and adaptive immunity, could play a role in this disorder. Objective: We aimed to study serum levels of MIF in a subset of children with autism and its relation to disease severity and important clinical manifestations of the disease. Methods: The study included 21 children and adolescents diagnosed with AD with a mean age of 6.9± 2.9 years. Patients were neurologically evaluated and categorized into those with mild to moderate autism and those with severe disorder. In addition to assessment of cognitive abilities and electroencephalogram performance, MIF levels were measured in the sera of included patients and were compared to those of a matched control group. Results: Levels of MIF were not significantly different in the patients and the control group. However, serum MIF was significantly reduced in patients with severe AD (z=2.197, P=0.029) compared to those with milder disease. Furthermore, there was a significant negative correlation between MIF levels and the degree of severity of the non-verbal communicative skills (r= -0.49, P=0.042). MIF levels were not different in patients with mental retardation, or abnormal electroencephalogram when compared to the rest of the patients. Conclusion: Our study suggests the presence of immune dysfunction in the form of derangement in serum MIF levels in children with AD. Its levels were specifically decreased in a subset of patients with severe disorder compared to those with mild to moderate disease. Decreased serum levels of MIF in patients with AD seem to be associated with worsening of the nonverbal communicative skills which is one of the disturbed behavioral parameters of AD. Further research is warranted to study the precise relationship of immune derangement and both the etiopathogenesis and the behavioral components of AD and its therapeutic implications."



Microglial activation state seems to be more important than microglial numbers, but reducing the amount of inflammatory microglia would be effective. Endotoxins{LPS], peripheral inflammation {esp gut}, mitochondrial dysfunction, and other factors driving the microglial damage being dealt with would be a more complete{enduring} and health giving solution.

Schizophrenia and Alzheimer’s disease risk linked to brain inflammation



Pivotal advance: inhibition of HMGB1 nuclear translocation as a mechanism for the anti-rheumatic effects of gold sodium thiomalate.

"Gold compounds such as gold sodium thiomalate (GST) can reduce the symptoms of rheumatoid arthritis (RA), although their mechanism of action is not well defined. As the proinflammatory mediator high mobility group box chromosomal protein 1 (HMGB1) may play a role in the pathogenesis of RA, we have performed in vitro studies to investigate whether GST inhibits HMGB1 release as the basis of its mode of action. Murine RAW 264.7 or human THP-1 macrophage cells were stimulated in culture with agents causing extracellular HMGB1 release, including LPS, IFN-gamma, polyinosinic:polycytidylic acid, IFN-beta, or NO in the presence of GST, ranging from 0 microM to 250 microM. Secretion and intracellular location of HMGB1 were assessed by Western blotting, HMGB1-specific ELISPOT assay, and immunofluorescent staining. In parallel, TNF and IFN-beta levels were analyzed by ELISPOT and/or ELISA. Supernatant NO production was analyzed by the Griess method. At pharmacologically relevant doses, GST inhibited the extracellular release of HMGB1 from activated macrophages and caused the nuclear retention of this protein; in contrast, no effects were observed on the secretion or production of TNF. Release of the key endogenous mediators of HMGB1 translocation, IFN-beta and NO, was inhibited by GST. This inhibition required gold, as sodium thiomalate did not affect the responses measured. Furthermore, gold chloride also inhibited release of HMGB1. Together, these results suggest a new mechanism for the anti-rheumatic effects of gold salts in RA and the potential of drugs, which interfere with intracellular HMGB1 transport mechanisms, as novel agents to treat RA."



Pivotal advance: inhibition of HMGB1 nuclear translocation as a mechanism for the anti-rheumatic effects of gold sodium thiomalate.


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