Gluten in Gut source of anti-brain antibodies

[halsgluten]

The Fall 2006 National Ataxia Foundation’s Generations newsletter reported a study that determined that anti-brain antibodies* are produced in the >intestines< of Gluten-Ataxia patients. Gluten-Ataxia patients produce these antibodies in response to eating wheat even when they have no intestinal symptoms.

This study also determined that at least two of these antibodies produce strong ataxia symptoms in mice. This strengthens the theory that Gluten-Ataxia is an autoimmune condition. (The remaining antibodies are not yet tested.)

The paper’s introduction is one of the best introductions to the links between gluten sensitivity and the nervous system.

Roughly 10% of American’s have some form of gluten sensitivity.

* Anti-brain antibodies = anti-gliadin, anti-tissue transglutaminase


Hal

Sources:
Enrico Tongiori, PhD, “Investigating Gluten-Dependent Autoimmunity as a possible cause of Sporadic Ataxia.” Generations, National Ataxia Foundation, Fall 2006.

Kenneth Fine, M.D, “Early Diagnosis Of Gluten Sensitivity: Before the Villi are Gone”, Transcript of a talk given by. to the Greater Louisville Celiac Sprue Support Group, June 2003.

[jcc]

Thanks Hal!

The tides...they are turning.

Seems like the gluten sensitvity folk keep taking steps forward. Glad to see it.

Cara

[annelb]

Here is something from the National Ataxia Foundation http://www.ataxia.org/research/studies/2006/naf-research-tongiorgi.aspx
We would like to investigate this disease in more detail and try to understand the mechanism by which sensitivity to gluten can cause ataxia. We will use the latest laboratory techniques to identify the anti-brain antibodies generated by the immune system activated by the ingestion of gluten.

What are anti-brain antibodies?
Anne

[jcc]

These are the antibodies I've seen referenced in ataxia.


CONCLUSIONS: Anti-tissue transglutaminase IgA antibodies are present in the gut and brain of patients with gluten ataxia with or without an enteropathy in a similar fashion to patients with celiac disease, latent celiac disease, and dermatitis herpetiformis but not in ataxia control subjects. This finding strengthens the contention that gluten ataxia is immune mediated and belongs to the same spectrum of gluten sensitivity as celiac disease and dermatitis herpetiformis.
Autoantibody targeting of brain and intestinal transglutaminase in gluten ataxia. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16476935&query_hl=10&itool=pubmed_docsum)
PMID: 16476935 Feb 2006


[Progressive myoclonic ataxia associated with antibodies against Purkinje cells in a celiac patient] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16454613&query_hl=10&itool=pubmed_docsum)
PMID: 16454613 Dec 2005

Patients with gluten ataxia have antibodies against Purkinje cells. Antigliadin antibodies cross-react with epitopes on Purkinje cells.
The humoral response in the pathogenesis of gluten ataxia (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11971090).


These are the ones I've seen referenced in PN:

Anti-tissue transglutaminase IgA antibodies in peripheral neuropathy and motor neuronopathy. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16774628&query_hl=2&itool=pubmed_docsum)
PMID: 16774628 July 2006

Transglutaminase-independent binding of gliadin to intestinal brush border membrane and GM1 ganglioside. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16766047&query_hl=25&itool=pubmed_docsum)
PMID: 16766047 Jun 2006

The neuropathy of celiac disease may be autoimmune and associated with anti-ganglioside antibodies.
Ganglioside reactive antibodies in the neuropathy associated with celiac disease (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12044986) June 2002

[halsgluten]

What are anti-brain antibodies?
Anne

Anne,

Anti-brain antibodies are autoimmune antibodies associated with brain tissue.
No doubt, there are many different anti-brain antibodies, but there are at least two types specifically associated with gluten.

Anti-gliadin antibodies bind specifically to the gliadin proteins that makes up much of wheat gluten. Someone with gluten sensitivity has elevated levels of anti-gliadin antibodies in the gut and frequently in the blood and other organs. Anti-gliadin antibodies also bind specifically to something in, on, or around Purkinje cells in the cerebellum – this binding sets up an immune reaction there.

Transglutaminase is an enzyme that breaks up proteins at points where the amino acid glutamine is located. There are elevated levels of transglutaminase in the gut and brain; particularly, higher levels are associated with disease; Celiac disease and degenerative brain diseases in particular. Anti-transglutaminase antibodies bind to transglutaminase, setting up an immune reaction wherever that occurs.

Interestingly, both anti-gliadin and anti-transglutaminase antibodies have associations with gluten and glutamine.

Wheat gliadin is rich in the amino acid glutamine. In fact, as a food, gliadin is uniquely rich in stretches of polyglutamine (long lengths of pure glutamine). Wheat gliadin actually accumulates in the intestines and other tissues of celiac much as other amyloids build up in many cases of degenerative brain diseases. Is it coincidence that these amyloids are also rich polyglutamine in several degenerative brain diseases (examples: Huntington’s disease, hereditary ataxia, Alzheimer’s disease, and Parkinson’s disease)?

Transglutaminase binds specifically to glutamine in protein and breaks the protein at those points. However, transglutaminase cannot break up POLYglutamine. Possibly, this is why transglutaminase tends to accumulate in tissues in Celiac disease and degenerative brain diseases. These peculiar accumulations of transglutaminase may be the reason for the development of anti-transglutaminase antibodies.

I know that’s a lot, but there is a lot more, real Nobel Prize Stuff.


Hal

[Zonulin]

Thanks for educating us, Hal. Very compelling research. I know there are many PubMed studies out regarding schizophrenia and celiac disease - I'll have to check out these others regarding ataxia, Parkinson's, etc.

Karen

[halsgluten]

I'll have to check out these others regarding ataxia, Parkinson's, etc.

Karen

To read up on the ataxia link is fairly simple, just search on the terms gluten and ataxia for starters.

From what I know, the Parkinson's link is more subtle. In genetic polyglutamine diseases there are genes that express the long-chain polyglutamine mutations (such as the toxins Huntingtin and Ataxin) that accumulate in the amyloid plaques. While the Parkinson's amyloids do contain polyglutamine toxin, there are no Parkinson's genes that express long-chain polyglutamine. In Parkinson's, there is a flaw in the ubiquitin-proteasome pathway that normally clears the short-chain polyglutamine (The Parkin protein is faulty). When this is the case, short-chain polyglutamine appears to accumulate and polymerize into long-chain polyglutamine.

Link:
http://www.jbc.org/cgi/content/abstract/jbc;278/24/22044

My hypothesis is that consumption of tissue penetrating gliadin from wheat accelerates any polyglutamine-moderated condition, perhaps completely modulating symptoms in mild cases.

Hal

[annelb]

Thanks - that explaination helped. I will have to read it and read the link tomorrow when my brain is more awake.
Anne

[jcc]

I think this Hal guy ;) will be good to have around :D. It will take a second reading for me, too!

Cara

[Marciab]

This is an excellent source of info on gluten ataxia ...

Thanks for all the work you put into this ... :)

Marcia