Rheumatoid Arthritis

Nurieva RI, Treuting P, Duong J, Flavell RA, Dong C. · Department of Immunology, and. Department of Comparative Medicine, University of Washington School of Medicine, Seattle, Washington, USA. · J Clin Invest. · Pubmed #12618524 links to  free full text

Abstract: CD4(+) helper Th cells play a major role in the pathogenesis of rheumatoid arthritis. Th cell activation, differentiation, and immune function are regulated by costimulatory molecules. Inducible costimulator (ICOS) is a novel costimulatory receptor expressed on activated T cells. We, as well as others, recently demonstrated its importance in Th2 cytokine expression and Ab class switching by B cells. In this study, we examined the role of ICOS in rheumatoid arthritis using a collagen-induced arthritis model. We found that ICOS knockout mice on the DBA/1 background were completely resistant to collagen-induced arthritis and exhibited absence of joint tissue inflammation. These mice, when immunized with collagen, exhibited reduced anti-collagen IgM Ab's in the initial stage and IgG2a Ab's at the effector phase of collagen-induced arthritis. Furthermore, ICOS regulates the in vitro and in vivo expression of IL-17, a proinflammatory cytokine implicated in rheumatoid arthritis. These data indicate that ICOS is essential for collagen-induced arthritis and may suggest novel means for treating patients with rheumatoid arthritis.

Simon LS. · Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis St Suite 4B, Boston, MA 02215, USA. · Best Pract Res Clin Rheumatol. · Pubmed #15301984 No free full text.

Abstract: The treatment of rheumatoid arthritis has changed dramatically in the last 10 years and in parallel the definition and expectations of patients and clinicians of the effects of disease-modifying anti-rheumatic agents has changed as well. Current expectations of efficacy now include improvement of signs and symptoms of disease activity as well as slowing, if not complete inhibition, of disease progression as measured by X-ray progression along with significant improvement in patient physical function. In addition, clinicians assess the safety profile of these agents more critically in an attempt to improve the risk:benefit profile. Drugs, such as methotrexate, sulfasalazine and leflunomide have provided patients with substantial relief of symptoms and improvement in terms of X-ray progression, but they have been hampered by the occurrence of significant adverse events along with the inability to maintain benefit for prolonged periods of time. With the increased understanding of the basic biological mechanisms of the disease process, there has been the introduction of four biological disease modifying therapies and other drugs into clinical practice, which have altered aspects of the risk:benefit ratio for patients with various rheumatic diseases.

Taira T, Matsuyama W, Mitsuyama H, Kawahara KI, Higashimoto I, Maruyama I, Osame M, Arimura K. · Division of Respiratory Medicine, Respiratory and Stress Care Center, Kagoshima University Hospital, Kagoshima, Japan. · Clin Exp Immunol. · Pubmed #17437420 links to  free full text

Abstract: Churg-Strauss syndrome (CSS) is a rare form of systemic vasculitis occurring in patients with asthma and hypereosinophilia; however, its mechanisms involved in the severe tissue inflammation with vasculitis are poorly understood. High mobility group box 1 (HMGB1) protein, originally identified as a DNA binding protein, also has potent pro-inflammatory and proangiogenic properties. In this study, we hypothesized that HMGB1 might be associated with CSS, and examined serum HMGB1 levels and compared those of asthma patients and healthy volunteers. We also investigated HMGB1 expression in the lesion, and eosinophil HMGB1 amount in CSS patients. We found that the serum HMGB1 levels in CSS patients were significantly higher than those of asthma patients and healthy volunteers. Eosinophils in the CSS lesion expressed HMGB1 and HMGB1 level in eosinophils from CSS patients was significantly higher than that of asthma patients, while there was no significant difference in HMGB1 levels in peripheral mononuclear cells. The serum HMGB1 level in CSS patients decreased after the steroid therapy, and showed significant positive correlations with several molecules, including soluble interleukin-2 receptor, soluble thrombomodulin, and eosinophil cationic protein in sera. We propose that HMGB1 might contribute to the pathogenesis of CSS.

Anonymous122576. · No affiliation provided · Best Pract Res Clin Rheumatol. · Pubmed #18592666 No free full text.

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