Rheumatoid arthritis and systemic lupus erythematosus as immune complex diseases.
Rheumatoid factors are 9s IgM autoantibodies directed against the hinge regions of 7s IgG's that have been changed consequent to their encounter with a foreign antigen, such as those produced by oral bacteria. Occasionally self-aggregating 7s IgG's serve this function. When these complexes are taken up by phagocytes in the joint, they form the "RA cell," a cell analogous to the LE cell of Hargraves. The circulating complexes, which activate complement cascades in the joint, are not specific for RA, being found in other rheumatic and autoimmune diseases as well as having a low prevalence in the normal population. Recently, other antigens resulting in autoimmune complex formation with greater specificity for RA have been described. These antibodies, known as anti-cyclic citrullinated peptide (anti-CCP) antibodies recognize citrullinated protein residues, which are present as antigenic determinants in patients with RA. This is in contrast to systemic lupus erythematosus (SLE), another autoimmune disease characterized by immune complexes in the systemic circulation. In the case of SLE, 7s IgG's directed against several nuclear antigens localize mainly in the kidneys and blood vessels. They also produce cerebral and pulmonary disease by activating complement systemically. Genetic defects in the complement cascade associated with SLE result in inadequate clearance of immune complexes as well as apoptotic blebs containing autoantigens.
Weissmann
Gerald
G
Biotechnology Study Center, New York University School of Medicine, New York, NY, USA. gerald.weissmann@nyumc.org
D056704:Adaptive Immunity; D000818:Animals; D000936:Antigen-Antibody Complex / Q000235:genetics / Q000276:immunology*; D034961:Antigens, Nuclear / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D003167:Complement Activation; D006801:Humans; D007105:Immune Complex Diseases / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D010456:Peptides, Cyclic / Q000276:immunology; D010586:Phagocytes / Q000276:immunology; D015398:Signal Transduction
D000936:Antigen-Antibody Complex; D034961:Antigens, Nuclear; D001323:Autoantibodies; D001324:Autoantigens; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide