autoantigen

An autoantigen is a self-derived molecule that is recognized as an antigen by the immune system in the setting of autoimmunity. Autoantigens can be intracellular or surface-expressed, and they may be proteins, lipids, or nucleic acids. When tolerance to these self-antigens fails, autoreactive B or T cells mount an immune response against them, leading to tissue damage.

Loss of self-tolerance may result from genetic predisposition (notably certain HLA alleles), environmental triggers, molecular mimicry, bystander activation, or epitope spreading. In many diseases, autoantigens are intracellular and become accessible only after cell injury or death, allowing presentation by antigen-presenting cells and the production of autoantibodies.

Common autoantigens include dsDNA and Smith antigen in systemic lupus erythematosus; Ro/SSA and La/SSB; thyroid peroxidase and thyroglobulin in autoimmune thyroid disease; the TSH receptor in Graves’ disease; acetylcholine receptor and MuSK in myasthenia gravis; GAD65 and IA-2 in type 1 diabetes; citrullinated proteins in rheumatoid arthritis; desmogleins in pemphigus; BP180 and BP230 in bullous pemphigoid.

Autoantibodies to autoantigens are widely used in diagnosis and disease classification, detected by immunoassays or indirect immunofluorescence, though they may be present in other conditions or in healthy individuals. Therapeutically, strategies sometimes target autoantibody production or activity, such as B cell–depleting therapy or plasmapheresis, alongside conventional immunosuppression.