The link between HLA genes and autoimmune disease: A comprehensive review

Autoimmune diseases (ADs) are a heterogeneous group of chronic inflammatory diseases, where immunological self-antigen tolerance is lost. These diseases are multifactorial and are a complex combination of environmental influences and genetic susceptibility. The human leukocyte antigen (HLA) complex, found in the major histocompatibility complex (MHC) on chromosome 6, is the most important genetic determinant of autoimmune susceptibility. The review gives a detailed discussion of the association between HLA genes and autoimmune diseases and discusses the molecular pathways of such associations. We discuss particular HLA-disease associations, such as the association between HLA-DRB1 and rheumatoid arthritis, HLA-DQ2/DQ8 and celiac disease, HLA-DR4 and HLA-DR3, and type1 diabetes HLA-B27 with ankylosing spondylitis. In addition, we comment on emerging patterns, such as allele-specific polarization of macrophages, and HLA, the gut microbiome, and autoimmune comorbidity. Such complicated processes are necessary to comprehend to develop effective immunotherapies and personalized medicine approaches in the treatment of patients with autoimmune disorders.