AofA Science Summary: The relationship between the increased frequency of serum antineuronal antibodies and the severity of autism in children
Eur J Paediatr Neurol. 2012 Jan 5. [Epub ahead of print]
The relationship between the increased frequency of serum antineuronal antibodies and the severity of autism in children.
Source
Autism Research and Treatment Center, AL-Amodi Autism Research Chair, Department of Physiology, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia; Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Abstract
BACKGROUND:
Autism may involve an autoimmune pathogenesis. Immunotherapy may have a role in autistic children who have brain auto-antibodies.
AIM:
This study aimed to investigate the frequency of serum antineuronal auto-antibodies, as indicators of the presence of autoimmunity to brain, in a group of autistic children. We are the first to measure the relationship between these antibodies and the degree of the severity of autism.
METHODS:
Serum antineuronal antibodies were measured, by indirect immunofluorescence technique, in 80 autistic children, aged between 6 and 12 years, in comparison to 80 healthy-matched children. The severity of autism was assessed by using the Childhood Autism Rating Scale.
RESULTS:
Autistic children had significantly higher percent positivity of serum antineuronal antibodies (62.5%) than healthy controls (5%), P<0.001. The frequency of the positivity of serum antineuronal antibodies was significantly higher in children with severe autism (87.5%) than children with mild to moderate autism (25%), P<0.001. Similarly, the frequency of the positivity of these antibodies was significantly higher in female children with autism (90%) than male autistic children (53.3%), P=0.001.
CONCLUSIONS:
Serum antineuronal antibodies were found in a subgroup of autistic children and they were significantly correlated to the severity of autism. Thus, autism may be, in part, one of the pediatric autoimmune neuropsychiatric disorders. Further wide-scale studies are warranted to shed light on the etiopathogenic role of antineuronal antibodies in autism. The role of immunotherapy in autistic patients, who are seropositive for antineuronal antibodies, should also be studied.
Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
PMID:
22226851
[PubMed - as supplied by publisher]
Theresa O you never ramble, and if you do it is productive rambling.
Tereasa Cornick; Looking forward to your next article. I watched a true doctumentary of a bike ride across the country raising awareness for AIDS. It documented a young man with AIDS and how the medicines affected him. His visit to the doctor to talk about perphrial pain that he was getting from one medicine made it impossible for him to continue on that drug, the next drug kept him close to a trash can, from throwing up while he was trying to help with the bikes, and the people that were riding.
God have mercy on our children; We are now between a rock and a hard place.
One Voice: Stop it before it happens makes perfect sense,but since when have they shown any common sense in this matter. They are telling parents with kids with Kawasakis maybe stop the vaccines for a little bit because the IVIG treatments won't let the MMR vaccine build immunity. Not that the kids have an overactive immune system and they don't need something else to make it react some more. Look at Dr Wakefield,------- and did you see that article about them complaining that pertussis is coming back because the whole cell vaccine was (oh wail and nash of teeth) was stopped and replaced with partial cell vaccine? By the way the partial cell still claims victims
Old, knarled James Cherry is still around defending and insisting on the return of the whole cell vaccine. I bet -- lots of money -- if he would bet --- that he has never had a tetanus shot (aka DPT shot) or he would be wearing a diaper, drooling in his plate of food, in a nursing home by now.
Posted by: Benedetta | January 12, 2012 at 08:25 AM
Hi Benedetta and Theresa-
This really describes my daughter- autoimmune, positive ANA, hormones, female, very affected. I am going to write more about this avenue of research as vaccines are hardly off the hook.
Thanks..
Posted by: Teresa Conrick | January 11, 2012 at 11:41 PM
Hi Son in Recovery-
Wanted to add these studies as for some, it is not the antibiotic killing the bacteria but the modulation of the immune system via reducing tumor necrosis factor-- something else I find interesting and wrote about regarding mercury exposure, viruses...and cancer.
J Chemother. 2009 Aug;21(4):396-402.
Azithromycin reduces tumor necrosis factor-alpha production in lipopolysaccharide-stimulated THP-1 monocytic cells by modification of stress response and p38 MAPK pathway.
Ikegaya S, Inai K, Iwasaki H, Naiki H, Ueda T.
Source
Division of Hematology and Cardiology, Faculty of Medical Science, Fukui University, Fukui, Japan.
Abstract
Macrolide antibiotics are known to have a variety of immunomodulatory effects in addition to antimicrobial activity, but the mechanisms of immunomodulation are still unclear. We investigated in vitro the effect of azithromycin on tumor necrosis factor alpha (TNF-alpha) production in lipopolysaccharide (LPS)-stimulated THP-1 cells, a human monocytic cell line, and compared the results with those for other macrolides, minocycline and ofloxacin. In the presence of LPS, treatment with azithromycin (AZM) resulted in a significant decrease in LPS-induced TNF-alpha production compared to that with other antimicrobial agents. the results of phosphorylation of three MAPKs, ERK, JNK and p38, indicated that the phospho-p38 level was reduced by AZM. Ikappab-alpha, an inhibitor of NFkappab, was not disrupted by the antibiotics. LPS-induced TNF-alpha release from THP-1 cells was inhibited in the presence of KNK437, a potent 70-kDa heat shock protein (HSP-70) inhibitor. Interestingly, the induction of HSP-70 by LPS was attenuated with the concurrent addition of AZM in the cells. AZM was found to restrain TNF-alpha production by monocytes at least in part by modifying the HSp-70 and p38 related signaling pathways to LPS stimulation.
And here you can see how it then would help with Lyme-
J Immunol. 2002 Jun 15;168(12):6352-7.
Murine Lyme arthritis development mediated by p38 mitogen-activated protein kinase activity.
Anguita J, Barthold SW, Persinski R, Hedrick MN, Huy CA, Davis RJ, Flavell RA, Fikrig E.
Source
Department of Biology, University of North Carolina, Charlotte, NC 28223, USA. [email protected]
Abstract
Borrelia burgdorferi, the Lyme disease agent, causes joint inflammation in an experimental murine model. Inflammation occurs, in part, due to the ability of B. burgdorferi to induce the production of proinflammatory cytokines and a strong CD4(+) T helper type 1 response. The mechanisms by which spirochetes induce these responses are not completely known, although transcription factors, such as NF-kappa B in phagocytic cells, initiate the proinflammatory cytokine burst. We show here that the mitogen-activated protein (MAP) kinase of 38 kDa (p38 MAP kinase) is involved in the proinflammatory cytokine production elicited by B. burgdorferi Ags in phagocytic cells and the development of murine Lyme arthritis. B. burgdorferi Ags activated p38 MAP kinase in vitro, and the use of a specific inhibitor repressed the spirochete-induced production of TNF-alpha. The infection of mice that are deficient for a specific upstream activator of the kinase, MAP kinase kinase 3, resulted in diminished proinflammatory cytokine production and the development of arthritis, without compromising the ability of CD4(+) T cells to respond to borrelial Ags or the production of specific Abs. Overall, these data indicated that the p38 MAP kinase pathway plays an important role in B. burgdorferi-elicited inflammation and point to potential new therapeutic approaches to the treatment of inflammation induced by the spirochete.
Posted by: Teresa Conrick | January 11, 2012 at 11:33 PM
It would be best not to introduce the antigen (eliminating the root cause of the problem)the first place,then the immune system would not be hyperstimulated to produce anti-neuronal antibodies.Once the immune system is damaged and the brain is involved repair will be very difficult and
expensive.I am thinking of the loss of quality of life/lives and
treatments which do not bring satisfactory results.I have to
agree with barbaraj.
Posted by: oneVoice | January 11, 2012 at 10:14 PM
I see what you're saying, Benedetta, and I think you're right, that the IVIG follows the plasma exchange. I hadn't realized that initially.
The thing about the plasma exchange that intrigued me was the idea that it could "clean out" the antibodies that were attacking the brain. Then again, if the cause of the anti-NMDA-R encephalitis isn't a tumor, I don't know how the doctors get the body to *stop* producing those antibodies. The idea of going through the process of plasma exchange on a regular basis is pretty scary.
I am so sorry about your sister-in-law. I wish someone had some good answers.
As for the diet, I read an interesting book recently (can't remember whether I've plugged it here before) called *The Jungle Effect,* providing information on "native" diets of several places in the world that are "cold spots" for particular diseases. The book is part case study, part biology textbook, and part cookbook. It does have some good suggestions regarding health-promoting foods (which foods and why), as well as some recipes to make native dishes.
One last thought on encephalitis: a childhood friend of mine who grew up to be a neurologist visited me over the weekend. (This is why I have had Teresa Conrick's articles on my mind.) My friend recently treated a patient who had anti-NMDA receptor encephalitis, which her initial physician failed to diagnose. After a few days in the hospital (and before my friend began treating her), the patient began exhibiting a fascination with water. Outside of the autism community, I had never heard anyone talk about a neurological disorder involving fascination with water. (Fear, yes--rabies--but never attraction.) Anyway, it kind of stuck in my mind.
This is the first time that I've thought that the puzzle logo made sense. In the past, I've always thought, well, we should just pull back from all the crazy not-really-tested stuff we do to kids (crazy vaccination formulation and schedule that starts before birth, feeding them GMOs, building mercury-emitting power plants near them, etc.). Now, though, I can see that scientists and doctors won't accept that they should ever stop doing something on the basis that it hasn't been shown to be safe. The puzzle is to discover and explain all the different pathways by which modern life makes us ill. Then, we can begin to undo the pathways to harm, and to treat the people who've been made ill.
Anyway, sorry for the ramble... Just thinking out loud about possible ramifications for the anti-neuronal antibody finding.
Posted by: Theresa O | January 11, 2012 at 09:27 PM
Thanks Thereasa O for explaining it furhter.
Thanks for pointing out it is experimental. I looked up what Therapeutic plasma exchange (TPE)was, and even if they use the patients own plasma they still get other people's plasma and put in too, as in using IVIGs after TPE. That means to me (and I am wrong most of the time) but they filter out the patients immune IgG thingeys and put in some one else's IgG thingeys. It is beginning to look like a cure amounts to about the same hurtles as treating cancer, and as expensive.
I will say that I don't think the IVIGs works.
But if they use this plasma exchange before using IVIGs it sounds reasonable it would help reteach the immune system how to act. BUt it still sounds pretty rough right up there with cancer treatments. ???
The reason I don't think the IVIGs works is ; Many with Kawasakis - have to have more than two or three treatments sometimes it works and sometimes it don't. Most of the time the docs will only treat once, at most twice, rarely three times, and then they have to reach for the steroids. Even if it does work - parents were reporting further complaints of on going fevers, and illness, only not as acute as typical Kawasakis.
We ourselves have already had one in the family take a series of IVIG treatments. She is my 40 year old sister-in-law. She was getting pneumonia every year and ending up at death's door. It did help that but really - it was no cure - it has not helped return her to health. Just this summer an MRI shows she is getting white pinprick spots on her brain, the doctor thinks(he thinks wrong) it it mini strokes and put her on plavix. She also this past summer now has developed mythenis gravis -- immune system is attacking the ATP basically.
Remember this was after the series of IVIG. And she has two boys with autism and another with bipolar. I would say it is the same disease.
Now plasma exchange and then followed with IVIG treatments? THis is getting pretty close to the all out battle like they do with cancer.
My sister-in-law like all Americans are waiting for the docs to tell us the kind of diet we are supppose to eat. Untill this past couple of months she finally gave in to my pleas and at least stopped eating bread and biscuits.
This looks like a long messes cure if there is a cure.
Posted by: Benedetta | January 11, 2012 at 08:07 PM
Here's what I do know - my 7 year old was diagnosed with PANDAS last year. We've been doing Biomed for 4 years along with a strict diet. Everything has helped inch by inch.... doctor tried Azithromycin as the antibiotic of choice this time and I have a totally new child. My 7 year old who has NEVER played with toys is beginning to play with them. And it's not just pushing around - it's actual pretend play. School's praised what he has been doing this week - "big gains" is the notes that have been forwarded to me. Skipping in OT - he's never been able to skip. Was my child diagnosed incorrectly?? His titers are off the charts... maybe once we get the inflammation down and his poor brain working properly I won't have an Autistic Kid - maybe just a PANDAS kid. BTW IVIG.. or what every it's called costs $1,000 per 10 pounds (Illinois doctor's office anyway).
Posted by: Son in Recovery | January 11, 2012 at 03:08 PM
Oh, Benedetta, I mean the therapeutic plasma exchange (also known as plasmapheresis), in which the patient's own plasma is taken out and cleansed and put back in. (I see that IVIG was used on some of the patients in the abstract I included, but I meant the plasma exchange therapy.)
In either case, I'm sure it's very expensive--I would imagine that multiple courses of plasma exchange using the patient's own blood would not be any cheaper than IVIG--but in the case of plasma exchange, you at least don't have the concern of "how clean is the material from the donors?" There is, of course, the concern of infection any time you open up the body.
I wouldn't think that a parent would self-finance plasma exchange (even if doctor were willing to go along with it); I meant, Has any researcher pursued it as a potential autism therapy?
My thinking is, in the case of anti-NMDA-R encephalitis, what is happening is that the body is attacking the brain (instead of the tumor or virus that it should be attacking), so options for treatment seem to be (1) dampening the immune system so that the attack is weakened or stopped and (2) cleaning out the attacking antibodies through plasma exchange. I know Teresa Conrick mentioned in a comment below her original post that the cases of anti-NDMA-R encephalitis are acute situations, rather than the chronic disease that autism seems to be... but I still wonder if the mechanism of injury (the body attacking those receptors in the brain) is the same, at least for some people with autism.
Posted by: Theresa O | January 11, 2012 at 01:51 PM
Theresa O
That is a lot of treatment!
IVIG -10,000 dollars - so I have heard that is what it cost, not to mention it is the plasma from a 1000 different people.
On top of that every bit of the blood to be taken out of the body and separated; put the blood cells back in and throw out the plasma.
WheW!
Posted by: Benedetta | January 11, 2012 at 12:19 PM
Hi, barbaraj,
Just a thought: This article reminds me of Teresa Conrick's recent two-part series on anti-NMDA receptor encephalitis and autism. True, many cases of anti-NMDA-R encephalitis are related to ovarian teratoma, but many are also possibly viral in origin--which, to me, doesn't get any viral exposure (including vaccines) "off the hook."
On that note, has anyone heard of TPE as a therapy for the symptoms (autism + anti-neuronal antibodies) described in the above article?
I mention TPE (despite its cost and the risk of infection) because of its apparent success in treating some cases of anti-NMDA-R encephalitis:
http://www.ncbi.nlm.nih.gov/pubmed/21898576
J Clin Apher. 2011 Dec;26(6):320-5. doi: 10.1002/jca.20311. Epub 2011 Sep 5.
Therapeutic plasma exchange for the treatment of anti-NMDA receptor encephalitis.
Pham HP, Daniel-Johnson JA, Stotler BA, Stephens H, Schwartz J.
Source
Department of Pathology and Cell Biology, Columbia University Medical Center and the New York-Presbyterian Hospital, New York, New York 10032. [email protected].
Abstract
Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is thought to be one of the common paraneoplastic-associated encephalitides. Between February 2001 and February 2011, nine patients were diagnosed with this disorder at Columbia University Medical Center: eight females (mean age 23 years) and one male (3 years of age). Four female patients had ovarian teratomas, which were removed as part of their treatment. Therapeutic plasma exchange (TPE) was used as one of the treatment modalities in addition to immunosuppressive therapy, including corticosteroids, intravenous immunoglobulin (IVIG), and/or rituximab. A total of 56 TPE procedures were performed in these patients on alternate days (range, 5-14 procedures/patient). Approximately 1 plasma volume (PV) was processed for all patients; 5% albumin and 0.9% normal saline were used as replacement fluid. Complications occurred in 20% of TPE procedures; 9% were possibly due to underlying disease. The remaining 11% of complications were hypotensive episodes that rapidly responded to either a fluid bolus or a vasopressor treatment. One patient demonstrated immediate clinical improvement after three TPE treatments, and four patients had significant improvement at time of discharge from the hospital. Long-term follow-up showed that early initiation of TPE appears to be beneficial, and patients who received IVIG after TPE did better than those who received IVIG before TPE. However, the number of patients in this series is too small to provide statistically significant conclusions. Overall, TPE is a relatively safe treatment option in patients with anti-NMDA-R encephalitis. Further studies are needed to elucidate the benefit of TPE in this disease. J. Clin. Apheresis, 2011.
Posted by: Theresa O | January 11, 2012 at 09:58 AM
The skeptic in me nags whenever I see a slightly reworked study in these publications. Doesn't this ring of PANDA...LYMES...all similar..am I missing the importance? I believe the direction many studies have taken over the years point toward autism as an autoimmune illness, and a smoke and mirror trick could take the "heat" off of vaccines. How will this effect future studies? In the last 14 yrs or so, this very similar finding with tics, behavioral issues, etc., hasn't promoted the identification of vaccine introduced antigens to the mix. Surely that should have been a focus, one to identify the disease process after exposure to vaccine introduced pathogens. Smoke and mirrors again?
Posted by: barbaraj | January 11, 2012 at 09:34 AM