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OBJECTIVE To investigate the safety and efficacy of MRA, a recombinant human anti-interleukin-6 (anti-IL-6) receptor monoclonal antibody of the IgG1 subclass that inhibits the function of IL-6, in patients with established rheumatoid arthritis (RA). METHODS A randomized, double-blind, placebo-controlled, dose-escalation trial was conducted in 45 patients(More)
Ninety-five patients with rheumatoid arthritis and 200 healthy controls were examined for HLA-D-related (HLA-DR) alloantigens. HLA-DRW4 was significantly more prevalent among the patients and was particularly common in those with a family history of the disease (77% of such patients had DRW4 compared with 34% of controls). Significantly fewer patients than(More)
We hope that this short review has produced convincing, although indirect, evidence that in the case of rheumatoid synovitis, the T cell is the conductor of an orchestra playing a tune written by an antigen-presenting cell. The tune develops and becomes modified with time, so that it is difficult to discern with clarity much of the original melody. We(More)
Understanding of the genetic basis of autoimmune diseases is currently incomplete. Cytokine gene polymorphisms warrant consideration as factors explaining variation in the human immune and inflammatory responses and as candidate susceptibility genes for related pathological states. Interleukin 12 (IL-12) is a key regulator of the polarisation of immune(More)
OBJECTIVES Cytokines, released from mononuclear cells (MNC) are mediators of joint destruction in rheumatoid arthritis (RA). The mechanisms of action of gold salts used in the treatment of RA are unknown. The aim of this study was to investigate cytokine expression and intensity of MNC infiltrate in the RA synovial membrane (SM) following treatment with(More)
In rheumatoid arthritis the synovial membrane has many of the characteristics of a hyperactive, immunologically-stimulated lymphoid organ. The basis of this hyperactivity is poorly understood. Highly specific antisera to human Ia-like (HLA-DR) antigens and monoclonal antibodies (OKT series) to various T-lymphocyte subsets were used to analyse both the(More)
OBJECTIVES To compare, by immunohistochemistry, the cellular and cytokine profile in rheumatoid arthritis (RA) and osteoarthritis (OA) synovial membranes (SMs). Synovium was obtained at knee arthroplasty from 10 patients with RA and 10 with OA. METHODS Synovial membranes were stained with a panel of monoclonal antibodies (MAb) to assess cytokine(More)
OBJECTIVE Constitutive differences between individuals in cytokine production may determine the variation in the course of inflammatory arthritis. METHODS The association between interleukin 10 (IL-10) production and joint destruction was studied by comparing IL-10 mRNA content in synovial biopsies from seven patients with destructive joint disease and(More)
OBJECTIVE To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase(More)