Could Tissue Transglutaminase Be The Autoantigen In Most Diseases And How Could This Be Related To A Gluten Intolerance?

December 28, 2010 · Filed Under Uncategorized 

Transglutaminases are very important enzymes. These enzymes are involved in many functions, such as tissue repair, signalling processes, cellular differentiation (cells become more specialized), matrix stabilization (tissue that provides support to cells), and apoptosis (biochemical change that causes death in cells that are not needed). Without it, tissue repair is hindered, unfavourable cellular changes can occur, abnormal cells could grow uncontrollably leading to cancer and signalling between cells could be affected. These changes could occur in any area of the body where the enzyme is not available.

How is tissue transglutaminase involved in a gluten intolerance? With celiac disease (CD), tissue transglutaminase 2 is damaged by antibodies in the bowel, antibodies against tissue transglutaminase 3 occur in dermatitis herpetiformis (DH) and antibodies attack tissue transglutaminase 6 in gluten ataxia. It seems reasonable to suspect that cross reactions to other types of transglutaminases could occur throughout the body in gluten intolerant individuals.

Like celiac disease, dermatitis herpetiformis and gluten ataxia, perhaps, immune responses to gluten and transglutaminase in the gut leads to autoimmune activity against various forms of transglutaminases throughout the body and this could result in different types of diseases. IgA and IgG antibodies against tissue transglutaminase could lead to inflammation and autoimmune damage in organs and tissues with transglutaminase. For example, transglutaminase can be found in the bowel, skin, bone, nervous system, lungs, heart, bladder, liver, pancreas, factor XIII (involved in clotting), prostate, uterus, etc. Theoretically, auto-antibodies against transglutaminases could cause inflammation and damage in these areas.

Hypothetically, immune reactions to gluten and cross reactions against tissue transglutaminase could be the underlying culprit in many types of syndromes, diseases, cancers (through disturbed apoptosis) and conditions. Inflammation and damage could result in symptoms throughout the body. I believe researchers need to take a closer look at the role transglutaminases have in the various areas of the body, how it is affected with different illnesses, and how the ingestion of gluten may be promoting a cross reaction against tissue transglutaminase in those illnesses.

With gluten as the underlying trigger, this type of reaction would be considered a type of non-celiac gluten intolerance if there was no intestinal villi damage. However, this non-celiac label may be questionable since intestinal mucosal changes have been found in patients with DH and in patients with gluten ataxia. Future research will help to clarify the similarities and differences between CD, DH, and non-celiac gluten intolerance. For me, it seems reasonable to suspect that all the various types of reactions to gluten are really just celiac disease presenting itself in various ways. Perhaps, it is time to re-define exactly what celiac disease is, instead of using different labels such as DH and non-celiac gluten intolerance.

For patients with diseases, syndromes, and other medical conditions, testing for CD along with antigliadin antibodies and testing for IgA deposits against transglutaminase 2 on intestinal biopsies may help to clarify if  gluten is involved.

More about tissue transglutaminase can be found in my book “Gluten Toxicity”.

References

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