title: Joint destruction in rheumatoid arthritis: biological bases.
abstract: The pathogenesis of rheumatoid arthritis (RA) can be explained through two main hypotheses: macrophage-fibroblast and macrophage-T cell interactions. The interplay between the various populations is influenced by a strong genetic component, which determines the severity of the disease in some cohorts of patients attending referral centers. The key question of the nature of the antigen(s) driving joint inflammation still remains unsolved. Exogenous antigens such as viruses or bacteria have long been searched for in the synovial fluids as well as in tissues, but convincing evidence of their pathogenic role are lacking. Data have been accumulated on the possible role of autoantigens, such as the spliceosomes, filaggrin, calpastatin, type II collagens, or other endogenous peptides, but no definite role regarding their potential contribution to the activation of T cells has been established. Once the process starts, a progressive recruitment of inflammatory T cells and macrophages into the joints occurs through a complex series of adhesion and migratory events. The key driving steps leading to synovial inflammation and cartilage destruction, along with the potential contribution of some key molecules, have been described, thus opening possible perspectives for a therapeutic approach.
authors.affiliation: Rheumatology Unit, United Medical School, Guy's Hospital, London, U.K.
authors.forename: G
authors.initials: G
authors.lastname: Kingsley
authors.forename: G S
authors.initials: GS
authors.lastname: Panayi
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D001324:Autoantigens / Q000276:immunology; D000091344:Filaggrin Proteins; D006801:Humans; D007596:Joints / Q000276:immunology / Q000473:pathology*; D008264:Macrophages / Q000276:immunology; D013585:Synovitis / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001324:Autoantigens; C000717249:FLG protein, human; D000091344:Filaggrin Proteins