Summary

In this review article, we evaluated experimental evidence supporting the pathogenic role of autoantibodies in rheumatic diseases and selected non-rheumatic autoimmune disorders. We conducted a narrative mechanistic review focusing on experimental studies, which employed passive transfer of patient-derived immunoglobulins or active immunization with defined autoantigens capable of reproducing disease-relevant phenotypes in vivo or ex vivo. Strong experimental evidence supports direct pathogenicity for several rheumatologic autoantibodies, including anti-citrullinated protein antibodies (ACPA), anti-myeloperoxidase (MPO) ANCA, anti-β2-glycoprotein I, anti-Ro/SSA, and anti-ribosomal P antibodies. These autoantibodies induce tissue-specific injury through mechanisms involving complement activation, Fcγ receptor engagement, inflammatory amplification, and antigen accessibility. Representative non-rheumatic autoimmune models, including pemphigus vulgaris, neuromyelitis optica spectrum disorder, and myasthenia gravis, further reinforce the generalizability of antibody-mediated tissue injury across autoimmune medicine. Passive transfer and active immunization studies provide compelling evidence that selected autoantibodies are not merely biomarkers, but active mediators of tissue injury under permissive biological conditions. These findings support the development of targeted therapies directed against pathogenic antibodies, complement pathways, and Fc-mediated effector mechanisms across rheumatic and autoimmune diseases.