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

December 28, 2010 · Filed Under Tissue Transglutaminase 

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.

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”.

“Gluten Toxicity” available at Amazon.com http://www.amazon.com/Gluten-Toxicity-Mysterious-Herpetiformis-Intolerance/dp/1453864113/ref=sr_1_5?ie=UTF8&qid=1295210451&sr=8-5

References

  1. Hasegawa G, Suwa M, Ichikawa Y, Ohtsuka T, Kumagai S, Kikuchi M, Sato Y, Saito Y. A novel function of tissue-type transglutaminase: protein disulphide isomerase. Biochem J 2003; 373:793-803.

  2. Kamaeva OI, Reznikov IP, Pimenova NS, Dobritsyna LV. Antigliadin antibodies in the absense of celiac disease. Klinicheskaia Meditsina, 1998; 76 (2):33-5.

  3. Griffin M, Casadio R, Bergamini CM. Transglutaminases: nature’s biological glues. Biochem J 2002;368:377-96

  4. Hill ID, Dirks MH, Liptak GS, Colletti RB, Fasano A, Guandalini S, Hoffenberg EJ, Horvath K, Murray JA, Pivor M, Seidman EG. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2005 Jan;40(1):1-19.

  5. Shane M. Devlin, MD, FRCPC, Christopher N. Andrews, MD, FRCPC, Paul L. Beck, MD, PHD, FRCPC. Celiac Disease. Canadian Family Physician, CME update for family physicians. May, 2004

  6. Mishra S, Murphy LJ. Tissue transglutaminase has intrinsic kinase activity: identification of transglutaminase 2 as an insulin-like growth factor-binding protein-3 kinase. J Biol Chem 2004;279:23863-8.

  7. Fesus L, Piacentini M. Transglutaminase 2: an enigmatic enzyme with diverse functions. Trends Biochem Sci 2002;27:534-9.

  8. Sakly W, Thomas V, Quash G and El Alaoui S. A role for tissue transglutaminase in alpha-gliadin peptide cytotoxicity. Clin Exp Immunol 2006;146:550-8.

  9. M Hadjivassiliou, RA Grünwald, GAB Davies-Jones. Gluten Sensitivity As A Neurological Illness. J Neurol Neurosurg Psychiatry 2002:72: 560-563.

  10. Sardy M, Karpati S, Merkl B, Paulsson M, Smyth N.Epidermal transglutaminase (TGase 3) is the autoantigen of dermatitis herpetiformis. J Exp Med.Mar 18 2002;195(6):747-57.

  11. Hadjivassiliou M, Aeschlimann P, Strigun A, Sanders DS, Woodroofe N, Aeschlimann D. Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase. Ann Neurol 2008 Sep;64(3):332-43.

  12. Hadjivassiliou M, Sanders DS, Grünewald RA, Woodroofe N, Boscolo S, Aeschlimann D. Gluten sensitivity: from gut to brain. Lancet Neurol. 2010 Mar;9(3):318-30.

Comments

13 Responses to “Could Tissue Transglutaminase Be The Autoantigen In Most Diseases And How Could This Be Related To A Gluten Intolerance?”

  1. Dr. Peter Osborne on December 28th, 2010 5:27 pm

    Great article! Thank you for pointing out the potential for gluten induced damage in multiple tissues of the body. This is a topic that is far too under recognized.

    Merry Christmas and Happy New Year!
    Peter

  2. Shelly on December 28th, 2010 7:48 pm

    Thank you Dr. Osborne! It is reassuring to know that there are doctors, like yourself, who understand the connection between gluten and their patient’s symptoms.

    Merry Christmas and Happy New Year to you and your family as well:)

    Shelly

  3. didier on January 2nd, 2011 2:33 am

    Hi Shelly,

    good job to point out that the immune response against TG isoforms are involved in pathogenesis of various disease. as a biological scxientist and CD patient, I follow closely the litterature about CD…and I am concerned to see how CD is unrecognized in many country. in France (my written english betrayed me) it is poorly recognized…hence people developped CD with compilcation…in my case it was a small bowell cancer…5Years ago at the age of 40. since then, while discussing with people at my workplace , some (7) have been also diagnose with CD…
    so keep informing people…
    happy new year to you

  4. Shelly on January 2nd, 2011 9:58 pm

    Thank you Didier for your comments and support. Yes, CD is very under recognized within the medical profession. So many are still undiagnosed and this can lead to many complications (like the one you experienced).

    It sounds like you are doing a great job of increasing awareness. Keep up the great work:)

    Happy New Year!
    Shelly

  5. Could Tissue Transglutaminase Be The Autoantigen In Most Diseases And How Could This Be Related To A Gluten Intolerance? « CeliacFacts on January 12th, 2011 6:36 am

    […] Read More… […]

  6. Shelly on January 12th, 2011 10:47 am

    Celiac Facts,

    So happy to see that this information is reaching others. Thank you for helping to spread the word!

    Shelly

  7. rick on January 16th, 2011 8:55 pm

    I’m happy to help. The content you produce here at Celiac Nurse is great!

    Rick

  8. Shelly on January 16th, 2011 9:11 pm

    Rick,

    Thank you so much for your support! I appreciate it:)

    Shelly

  9. Beth Triner on March 16th, 2011 4:01 pm

    tTG2->bowel, tTG3->skin, tTG6->nerves

    Do you know which isoform — tTG 2, 3, or 6 — is detected by current labkits used to test for CD? For example someone with DH or someone with gluten ataxia may be serologically negative because the kit only detects tTG2. Is this a possibility?

  10. Shelly on March 20th, 2011 6:01 pm

    Beth,

    Yes, you are right. The current lab kits for celiac disease (kits that I’m aware of) only test for for tTG2 so only the celiac type of gluten intolerance would be picked up. The other types of gluten intolerance could be missed. The diagnosis chapter in my book discusses this in more detail.

    I hope this helps:)
    Shelly

  11. maddieaddie on May 26th, 2011 7:19 am

    Shelly,

    Do you have any thoughts on the use of transglutaminase of microbial and pig origin in the use of meat preparation. It is commonly referred to as “meat glue” and is used in composite meat products and to form whole steaks from smaller cuts. I am concerned that it may contribute to celiac symptoms, but that it is hard to avoid due to lack of labeling requirements.

    Thank you!

  12. Shelly on June 5th, 2011 1:00 pm

    This is an interesting question:) With a gluten intolerance, the immune system initially reacts to gluten and then can cross react with transglutaminase (an enzyme in our body). Once people are eating a strict gluten-free diet, the antibodies against transglutaminase generally decrease or disappear.

    Theoretically, if no gluten is being consumed then I would suspect that there shouldn’t be any antibody cross reactions against the transglutaminase in the meat. However, if someone is still consuming gluten (even trace amounts), then there would likely be circulating antibodies against transglutaminase still in the body. In this situation, it seems reasonable to suspect that these antibodies could cross react with other sources of transglutaminse in our food.

    Definitely, more research should be done to look at this possibility! For the newly diagnosed or people with persistently elevated antibody levels (against gluten and transglutaminase), this may be something worth considering and discussing with their doctors. Thank you for your insightful question:)

    Best regards,
    Shelly Stuart

  13. Terry-Ann on August 19th, 2014 8:32 am

    Hi Shelly
    My dad has had celiac for 28 yrs. Throughout that time he has been mostly noncompliant. He has major sinus issues and breathing issues.Last week he was put on ventilator for 6 days. In that time he had 2 bronchoscopies done. These bronchs showed copious amounts of thick mostly clear mucous.Physio and RT are working with him. He came off the vent and was doing well for a day or so. Now he’s back on 65% O2 & he can’t get the mucous up anymore its so thick again. My question is I know he has asthma but could the thick secretions be connected to his celiac & if so how do you go about treating it.

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