Autoantibodies

Autoantibodies are antibodies produced by the immune system that target the body’s own tissues and components. They arise when B cells escape or override normal tolerance to self-antigens. While they can be markers of autoimmune disease, autoantibodies are also found in some healthy people and may reflect aging, infection, or nonspecific immune activation without causing symptoms.

Several mechanisms contribute to their development, including genetic predisposition (notably certain HLA alleles), environmental triggers, and immune processes such as molecular mimicry, bystander activation, and epitope spreading. Some autoantibodies are present in low levels with no apparent disease, whereas others are closely linked to specific conditions or subtypes.

Autoantibodies are widely used as diagnostic and prognostic biomarkers. Detection methods include indirect immunofluorescence (often for antinuclear antibodies, ANA) and various immunoassays (ELISA, chemiluminescence) for specific antibodies. Common associations include ANA with a range of autoimmune diseases, anti-dsDNA and anti-Smith antibodies with systemic lupus erythematosus, antiphospholipid antibodies with antiphospholipid syndrome, anti-CCP with rheumatoid arthritis, and antibodies such as anti-TPO or anti-thyroglobulin with autoimmune thyroid disease. Other examples include anti-centromere, anti-Scl-70 (topoisomerase I), and anti-Jo-1.

Pathogenic mechanisms include immune complex deposition, activation of the complement system, and disruption or modulation of normal receptor signaling, which can contribute to tissue injury. In some diseases, autoantibody profiles help classify subtypes or guide prognosis; in others, the presence of autoantibodies informs monitoring or therapeutic decisions. Importantly, a positive autoantibody test does not by itself establish a diagnosis without clinical context.