Association between Celiac Disease and Human Leukocyte Antigen

Abstract

Coeliac disease is an immunologically mediated disease of the small intestinal mucosa, characterized by flattening of the small intestinal villi, increased numbers of intra-epithelial lymphocytes and inflammatory cell infiltrates in the lamina propria, resulting in gut damage and nonspecific malabsorption of nutrients. The disease is elicited by ingestion of gluten, a protein found in several cereals, principally wheat, but also barley and to a lesser extent, oats. Successful treatment is avoidance of dietary gluten. Long-standing evidence suggests a T-cell-mediated response to peptides derived from the gliadin fraction of wheat gluten, leading to immunologically mediated intestinal injury in genetically susceptible individuals. The strength of this genetic susceptibility is indicated by 80% disease concordance in monozygotic twins and 11% concordance in dizygotic twins, and HLA has long been implicated as strongly associated with susceptibility to CD. Various studies in the late 1980s and early 1990s, including those under the auspices of the International Histocompatibility Workshops, lead to definition of the DQA1*05:01, DQB1*02:01 heterodimer, encoded in cis or trans, as being the principal HLA association.