Post-Translational Modified Neoantigens in Autoimmune Diseases: Challenges of Immune Tolerance

Autoimmune diseases, like spondyloarthritis (SpA) and rheumatoid arthritis (RA), have a high incidence and disability rate and are major diseases that seriously endanger human health. The pathogenesis of autoimmune diseases involves the interaction among genetic factors, environmental factors, and immune disorders. The post-translational modified neoantigens are the key nodal of these three factors. Under the intervention of the external environment, changes in metabolic status in vivo induce metabolite-related post-translational modifications (PTMs). These PTM proteins and peptides, after being presented by human leukocyte antigen (HLA) molecules of specific genotypes, can trigger autoreactive T cell expansions which are antigen-specific and then develop into autoimmunity. Such biological processes are a great challenge to the immune tolerance status and can be an important cause of autoimmune diseases.