Autoantigens and immune pathways in rheumatoid arthritis.
Rheumatoid arthritis (RA) is a major systemic autoimmune disease. A plethora of putative autoantigens has been described by the reactivity of antibodies present in the sera of patients. Despite this there is little evidence implicating most of them in its pathogenesis. Autoantigens fall into two major groups: first, those that are associated with the joint, such as collagen type II, human chondrocyte glycoprotein 39, and proteoglycans, for which a pathogenic role is easily understood; and second, those proteins not associated with the joint. Of these there are three groups: (1) highly conserved foreign antigens with human homologues, such as heat shock proteins (HSPs), in which the initiating antigenic stimulus may be through infection; (2) post-translationally altered proteins, such as citrullinated filaggrin, to which autoantibodies show high specificity but low sensitivity for RA and immunoglobulin G; and (3) ubiquitous proteins, such as glucose-6-phosphate isomerase, p205, and HSPs secreted during stress, such as BiP. The mechanisms by which such ubiquitous antigens cause pathology predominantly in the joints are difficult to understand. Autoantibodies, such as rheumatoid factors, that form immune complexes resulting in activation of phagocytic cells or the complement system, may cause joint pathology by deposition in the joints. Such an explanation, however, is not available for all of these autoantigens. It is possible that pathology may be the outcome of disturbed immunoregulation.
Corrigall
Valerie M
VM
Department of Rheumatology, GKT School of Medicine, 5th Floor, Thomas Guy House, Guy's Hospital, London SE1 9RT, UK. valerie.corrigall@kcl.ac.uk
Panayi
Gabriel S
GS
D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D000091344:Filaggrin Proteins; D006801:Humans; D015398:Signal Transduction / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; C000717249:FLG protein, human; D000091344:Filaggrin Proteins