These peptides are modified by tTG in two ways, deamidation or transamidation.Deamidation is the reaction by which a glutamate residue is formed by cleavage of the epsilon-amino group of a glutamine side chain. Transamidation, which occurs three times more often than deamidation, is the cross-linking of a glutamine residue from the gliadin peptide to a lysine residue of tTg in a reaction that is catalysed by the transglutaminase. Crosslinking may occur either within or outside the active site of the enzyme. The latter case yields a permanently covalently linked complex between the gliadin and the tTg. This results in the formation of new epitopes believed to trigger the primary immune response by which the autoantibodies against tTg develop.Stored biopsies from people with suspected coeliac disease have revealed that autoantibody deposits in the subclinical coeliacs are detected prior to clinical disease. These deposits are also found in people who present with other autoimmune diseases, anaemia, or malabsorption phenomena at a much increased rate over the normal population. Endomysial components of antibodies (EMA) to tTG are believed to be directed toward cell-surface transglutaminase, and these antibodies are still used in confirming a coeliac disease diagnosis. However, a 2006 study showed that EMA-negative people with coeliac tend to be older males with more severe abdominal symptoms and a lower frequency of "atypical" symptoms, including autoimmune disease. In this study, the anti-tTG antibody deposits did not correlate with the severity of villous destruction.
As of July 2017, the Vatican still outlawed the use of gluten-free bread for Holy Communion. Passover
The Jewish festival of Pesach (Passover) may present problems with its obligation to eat matzo, which is unleavened bread made in a strictly controlled manner from wheat, barley, spelt, oats, or rye. This rules out many other grains that are normally used as substitutes for people with gluten sensitivity, especially for Ashkenazi Jews, who also avoid rice. Many kosher-for-Passover products avoid grains altogether and are therefore gluten-free. Potato starch is the primary starch used to replace the grains. Spelling
Coeliac disease is the preferred spelling in British English, while celiac disease is typically used in North American English. Research directions
The search for environmental factors that could be responsible for genetically susceptible people becoming intolerant to gluten has resulted in increasing research activity looking at gastrointestinal infections. Research published in April 2017 suggests that an often-symptomless infection by a common strain of reovirus can increase sensitivity to foods such as gluten.Various treatment approaches are being studied, including some that would reduce the need for dieting. All are still under development, and are not expected to be available to the general public for a while.Three main approaches have been proposed as new therapeutic modalities for coeliac disease: gluten detoxification, modulation of the intestinal permeability, and modulation of the immune response.Using genetically engineered wheat species, or wheat species that have been selectively bred to be minimally immunogenic, may allow the consumption of wheat.