The Human Leukocyte Antigen (HLA) has a crucial role in the development and pathogenesis of coeliac disease (CD). The genes HLA-DQA1 and HLA-DQB1, both lying in this region and encoding the HLA-DQ heterodimer, are the main genetic predisposing factors to CD. Approximately 90% of CD patients carry the heterodimer HLA-DQ2.5, leaving only a small proportion of patients with lower risk heterodimers (HLA-DQ8, HLA-DQ2.2 or HLA-DQ7.5). These HLA-DQ molecules act as receptors present in the surface of antigen presenting cells and show high affinity for deamidated gluten peptides, which bind and present to CD4+ T cells. This triggers the immunological reaction that evolves into CD. Since specific HLA genetics is present in almost the totality of CD patients, HLA typing has a very high negative predictive value, and it can be used to support diagnosis in specific scenarios. HLA risk has been associated to different CD-related features, such as age at onset, clinical outcomes, antibody levels and grade of histological lesion; but further research is needed. HLA-DQ genotypes have been also suggested to modulate the composition of the gut microbiota.
Keywords: Diagnosis; Genetic susceptibiity; HLA; Pathogenesis; Phenotypic association.
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