Immunogenetics of non celiac gluten sensitivity

The immunogenetics of coeliac disease (CD) has advanced from “Bench to Bed” in the sense that HLA-DQ typing is now an established part of the diagnostic armamentarium. The configuration characteristics and the specificity of the HLA-DQ2, (1) -DQ8 (2, 3) and –DQ9 (4, 5) allow the binding of small peptides that cannot be further digested by the absence of specific human intestinal enzymes (6, 7). These peptides are derived from wheat (gliadins and glutenins), barley (hordeins), rye (secalins), oats (avenines) and hybrids of these grains, such as kamut and triticale and bind to HLA molecules, in particular when deamidated by tissue transglutaminase (8, 9).The stimulation of dendritic and T cells contribute to produce the spectrum of the characteristic changes of the duodenal and jejunal mucosa present in (CD). These changes lead to intestinal symptoms and autoimmune reactions that may affect extraintestinal organs. It is also known that the immune response can remain dormant. Environmental elements trigger the disease and, as opposed to what was thought to be a lifelong disease, it may be transitory (10, 11). Genomics studies have revealed that many other genes are involved in the modulation of the immune response but these findings have not yet transcended into the clinic workup, although 57 additional non HLA variants have improved the identification of potential CD patients (12). In the past 10 years it has become clear that there is a group of conditions related to gluten consumption. Foremost among them are three types: a) the least common is wheat allergy; although the estimated prevalence of food allergy among adults in Western Europe is thought to be between 1 and 2%, with the frequency in infants being greater (approximately 5%). b) The autoimmune form, the best characterized, includes CD, dermatitis herpetiformis, and gluten ataxia and c) sensitivity to gluten, which is possibly immune-mediated and now the most common (13). Recent studies of the immunogenetics of different forms of wheat allergy have implicated beta adrenergic receptor polymorphisms (14) and Tollreceptor 4 (15). IL-18 polymorphisms were significant associated with the rate of sensitization to wheat flour (16) and more recently IL-4 receptor alpha polymorphisms have been found to be associated in bakery workers (17, 18).