Autoantigens

Autoantigens are self-derived molecular targets recognized by the immune system in autoimmune diseases. They are components of the body's own tissues or cells that, under certain conditions, become the focus of an immune response. Autoantigens can be intracellular or extracellular, and their recognition by autoreactive B or T cells can contribute to tissue injury.

Mechanisms leading to autoimmunity include loss of self-tolerance, molecular mimicry where foreign antigens resemble self components, and epitope spreading that broadens reactivity. Post-translational modifications such as citrullination or phosphorylation can create neoepitopes that escape tolerance. Sequestered antigens released during tissue damage or apoptosis can also become targets.

Autoantigens are often categorized as organ-specific, such as thyroid peroxidase or insulin, or systemic, such as double-stranded DNA, histones, SSA/SSB or glutamate decarboxylase. In rheumatoid arthritis, citrullinated proteins are prominent autoantigens; in systemic lupus erythematosus, anti-dsDNA and anti-Sm are common. Autoantibodies against erythrocyte, platelet, or basement membrane components are involved in related diseases.

Autoantigens are central to diagnostic testing. Autoantibody assays—indirect immunofluorescence, ELISA, and immunoblot—detect antibodies against specific autoantigens. The presence and pattern of autoantibodies can aid diagnosis, influence prognosis, and, in some diseases, precede clinical onset by years.

Therapeutically, targeting autoreactive B cells or modulating tolerance is an area of study. Treatments such as B-cell depletion or tolerance-inducing approaches aim to reduce autoantigen-directed responses and limit tissue damage.