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Immunodominant Peptide Identified in Celiac Disease

Nat Med 2000;6:337-342. (March 1, 2000)
see also: BMJ 2000;320:736 (March 18, 2000)

(Celiac.com 03/17/2000) Researchers in Britain have identified a dominant epitope of the A-gliadin protein of wheat that is linked to the cause of celiac disease. The findings could eventually influence the diagnosis and treatment of the disease. With the new information Wheat could be genetically engineered to be non-toxic for celiacs, according to Dr. Robert P. Anderson. Also, modified versions of T cell epitopes can have unique antagonistic effects that switch off particular immune responses. The identification of this peptide could be used to develop a blood tests to better diagnose celiac disease, and could also be used to better test food for celiac toxicity.

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Dr. Anderson and his University of Oxford colleagues used a series of 15 amino acid peptides along the A-gliadin sequence (alpha gluten) to stimulate in patients with celiac disease their peripheral blood mononuclear cells, or PBMCs. The peptides were either unmodified or were treated with tissue transglutaminase, which, in the presence or absence of lysine, will convert glutamine to glutamate.

Researchers successfully stimulated PBMCs in celiac patients who were in remission due to a gluten-free diet with a gluten challenge. Patients were fed wheat bread for either a half day, 3 days, or 10 days, and healthy, non-celiac patients that were fed wheat bread each day for 4 weeks were used as controls. The researchers successfully produced PBMCs from the celiac disease group, who secreted interferon-gamma 6-8 days later, in response to a particular pool of A-gliadin peptides, which had been treated with tissue transglutaminase. A 17-amino-acid peptide, corresponding to the partially deamidated peptide of A-gliadin amino acids 57-73, was optimal for inducing the interferon-gamma secretion, and the responses were restricted to those with HLA-DQ2.

According to Dr. Anderson: On a more general level, the finding that a host enzyme modifies peptides that are then recognized by the immune system suggests that searching for epitopes important in disease may be more complex than simply reading off protein sequences from sequenced genes. Further, modification of the peptide by tissue transglutaminase that is present in the intestinal lining increases binding of the peptide to HLA-DQ. The researchers also point out that T cells that are responsive to the same A-gliadin peptide are readily induced in celiac disease despite many years of following a gluten-free diet, which indicates a persistence of memory T cells that could be caused by continuing exposure to trace amounts of gluten. The researchers only looked at the A-gliadin peptide, and point out that there is a possibility that other peptides that are structurally unrelated to A-gliadin are also important in celiac disease.

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Hi wondering if someone could help. my daughter has mildly raised TTG levels and the gliadine levels, she has one Coeliacs gene, but her biopsy came back negative. We have kept her off gluten (and low dairy) for nearly a year to see if her symptoms improved. They haven't. But I don't know if they are related to gluten specifically. Just wondering if anyone has other suggestions that may be going on with her. Her symptoms are: - Short stature, she's nearly 9 and my 6 year old boy is nearly bigger than her - bumps on back of her arms - urine leaking and occasional soiled pants, which could be from constipation she has at time's - sticking out stomach - dry patchy rashes on her face - joint pain sporadically - vomits every 6 weeks, but hasn't had gluten and seems to be no food connection - reoccurring thrush She had gluten last night at a party and was fine today. I'm a bit lost and not sure where else to turn. Thanks for any help.

We have gone gluten free, our whole house, as of a month ago. It was pretty seamless since I had been gluten-free for 5 months last year. I have found many good recipes, and my picky husband and one of my boys who is also a picky eater, even prefer many gluten-free recipes to the regular ones. My husband did see my point about the size of the gluten protein means nothing. Its a gluten protein period, that's what you are avoiding. It doesn't matter if its hiding in the scratch of your baking sheet and you can't see it. You can't see the wind, but it's still there. I hear you on the anemia. I've been anemic for several years, I just thought it as because I was getting a little older. Has your anemia gone away or do you still have problems with it?

Ennis, it is made out of metal, coated with plastic I think. You have such a hard time, my heart really hurts for you. But you are such a support to those on this board, and a great teacher for those of us who are new.

Thanks everyone! I think its hard for people to fully accept because they cant see the damage it does every time you get glutened. It's invisible. Im glad to know I wasnt being paranoid. I sure was when I was first diagnosed. I laugh at myself now, but its a pretty steep learning curve.

FYI......anxiety is a common symptom with celiac disease and NCGI. It seems to resolve on a gluten-free diet. ?