Tissue-specific autoantigens

Tissue-specific autoantigens are a diverse class of endogenous molecules, primarily proteins, that are localized to specific organs or tissues and serve as the primary targets of misdirected immune responses in organ-specific autoimmune diseases [1, 7]. Unlike systemic autoantigens, which are ubiquitously expressed, these antigens are restricted to particular sites, such as the pancreatic beta cells in Type 1 Diabetes (e.g., insulin, GAD65) or the central nervous system in Multiple Sclerosis (e.g., myelin basic protein) [6, 14]. The breakdown of self-tolerance leads to the activation of autoreactive T and B cells that recognize these antigens, resulting in chronic inflammation and progressive tissue destruction [8, 17]. Therapeutic strategies targeting tissue-specific autoantigens focus on restoring immune homeostasis through antigen-specific immunotherapy (ASI), which aims to "re-train" the immune system to tolerate these molecules without inducing global immunosuppression [4, 11]. While many antigen-specific approaches, such as peptide-based vaccines and tolerogenic dendritic cell therapies, are currently in clinical or preclinical development, standard treatment often remains limited to non-specific immunosuppressive agents that manage symptoms rather than the underlying cause [6, 11]. Monitoring these autoantigens and their corresponding autoantibodies is critical for the diagnosis and management of various autoimmune conditions [10, 15].

Other names

Organ-specific autoantigensSelf-antigensTissue-restricted autoantigensAutoantigens

Induction of antigen-specific immune tolerance through T-cell anergy, clonal deletion, or the expansion of regulatory T cells (Tregs); suppression of autoreactive B-cell activation; and neutralization of circulating autoantibodies.