Pathogenesis of autoimmune diseases caused by genetic variants of co-stimulatory molecules for antigen presentation

Abstract

Autoimmune diseases are caused by a breakdown in the tolerance that evades immune responses to self-antigens, and it is assumed that genetic and environmental factors collectively contribute to their development. To date, numerous disease susceptibility gene loci have been identified using comprehensive genome analysis methods such as genome-wide association studies (GWAS). Among these, genes encoding co-stimulatory molecules that play an important role in antigen presentation from Human Leukocyte Antigen (HLA) to T cell antigen receptor (TCR) have relatively many disease susceptibility gene loci common to multiple autoimmune diseases. It has been revealed that CD80, ICOSLG, CD40, CD58, CD28, CTLA4, and PDCD1, are involved in autoimmune diseases because of specific genetic variants by the post-GWAS analyses using in silico analyses and the genome editing technologies such as CRISPR/Cas9.