Leukapheresis and pathogenetic mechanisms in rheumatoid arthritis.
Rheumatoid Arthritis is a chronic, usually progressive inflammatory disorder of joints in which the immune system plays a central role in the pathogenesis. In its classic form, the synovial tissues from severely affected joints are densely infiltrated with HLA-DR bearing T-lymphocytes (primarily OKT4+/Leu3+ subset) and macrophage-like cells. Moreover, these tissues, as demonstrated by ex vivo culture, spontaneously produce high levels of a multitude of inflammatory mediators, such as collagenase, PGE2, interleukin 1 and fibroblast activating factors, indicating that the cells infiltrating the synovium are "activated". The action of these various inflammatory mediators on different target substances or cells (collagen, fibroblasts, chondrocytes, osteoclasts, etc.) most likely produce the characteristic pattern of joint pathology. Recent data indicate that this classic form of synovitis tends to be associated with peripheral anergy and other qualitative and quantitative abnormalities in the peripheral blood mononuclear cells. Repeated leukapheresis can induce substantial, although transient, clinical improvement in patients with these classic features, probably as a consequence of disrupting T-lymphocyte traffic. Rheumatoid synovitis, however, is highly heterogeneous, but can be categorized into subsets. For example, a subset of patients with highly active clinical rheumatoid arthritis exists which do not exhibit the classic features of disease. Synovial tissues from this patient subset are sparsely infiltrated by T-lymphocytes but contain mainly macrophages and fibroblasts, as well as prominent lining layer fibrin deposition.(ABSTRACT TRUNCATED AT 250 WORDS)
D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D006801:Humans; D007111:Immunity, Cellular; D007937:Leukapheresis; D008264:Macrophages / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology