title: Rheumatoid arthritis and the complement system.
abstract: Complement activation contributes to a pathological process in a number of autoimmune and inflammatory diseases, including rheumatoid arthritis (RA). In this review we summarize current knowledge of complement contribution to RA, based on clinical observations in patients and in vivo animal models, as well as on experiments in vitro aiming at elucidation of underlying molecular mechanisms. There is strong evidence that both the classical and the alternative pathways of complement are pathologically activated during RA as well as in animal models for RA. The classical pathway can be initiated by several triggers present in the inflamed joint such as deposited autoantibodies, dying cells, and exposed cartilage proteins such as fibromodulin. B cells producing autoantibodies, which in turn form immune complexes, contribute to RA pathogenesis partly via activation of complement. It appears that anaphylatoxin C5a is the main product of complement activation responsible for tissue damage in RA although deposition of membrane attack complex as well as opsonization with fragments of C3b are also important. Success of complement inhibition in the experimental models described so far encourages novel therapeutic approaches to the treatment of human RA.
authors.affiliation: Lund University, Department of Laboratory Medicine, University Hospital Malmö, Malmö, Sweden.
authors.forename: Marcin
authors.initials: M
authors.lastname: Okroj
authors.forename: Dick
authors.initials: D
authors.lastname: Heinegård
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.forename: Anna M
authors.initials: AM
authors.lastname: Blom
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D003167:Complement Activation / Q000502:physiology*; D051056:Complement Inactivating Agents / Q000627:therapeutic use; D003165:Complement System Proteins / Q000502:physiology*; D006801:Humans
chemical_list: D051056:Complement Inactivating Agents; D003165:Complement System Proteins