Pathogenic autoantigens and circulating autoantibodies

Pathogenic autoantigens and circulating autoantibodies represent a broad category of molecular drivers in autoimmune diseases rather than a single therapeutic target. Autoantigens are endogenous molecules, such as proteins, nucleic acids, or lipids, that are mistakenly recognized by the immune system as foreign, leading to a breakdown in self-tolerance (Vanderlugt & Miller, 2002, Nature Reviews Immunology). Circulating autoantibodies are the effector immunoglobulins produced by B-lineage cells that specifically bind to these autoantigens, causing tissue damage through complement activation, recruitment of inflammatory cells, or direct functional interference with cellular receptors (Ludwig et al., 2017, Frontiers in Immunology). In clinical practice, these molecules serve as critical diagnostic and prognostic biomarkers for conditions like systemic lupus erythematosus, rheumatoid arthritis, and myasthenia gravis. Therapeutic intervention focuses on reducing the load of these pathogenic antibodies through plasma exchange, inhibiting their recycling via FcRn blockers, or depleting the B-cell populations responsible for their secretion (Hofmann et al., 2018, Frontiers in Immunology). Because this term encompasses thousands of distinct antigen-antibody pairs across diverse pathologies, it is considered a disease mechanism category rather than a specific protein target.

Other names

Self-antigensAutoantigensAutoantibodiesHumoral autoantigensEndogenous antigens

Therapeutic strategies include B-cell depletion (e.g., anti-CD20) to reduce autoantibody production, neonatal Fc receptor (FcRn) inhibition to accelerate the clearance of pathogenic IgG, and B-cell activating factor (BAFF) inhibition to reduce B-cell survival (Ludwig et al., 2017, Frontiers in Immunology; Gable et al., 2020, Drugs).