Exploring the HLA complex in autoimmunity: From the risk haplotypes to the modulation of expression

Abstract

The genes mapping at the HLA region show high density, strong linkage disequilibrium and high polymorphism, which affect the association of HLA class I and class II genes with autoimmunity. We focused on the HLA haplotypes, genomic structures consisting of an array of specific alleles showing some degrees of genetic association with different autoimmune disorders. GWASs in many pathologies have identified variants in either the coding loci or the flanking regulatory regions, both in linkage disequilibrium in haplotypes, that are frequently associated with increased risk and may influence gene expression. We discuss the relevance of the HLA gene expression because the level of surface heterodimers determines the number of complexes presenting self-antigen and, thus, the strength of pathogenic autoreactive T cells immune response.