Rheumatoid Arthritis: Dai M

Yang HP, Dai M, Zhang DH. · Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. · Zhongguo Shi Yan Xue Ye Xue Za Zhi. · Pubmed #17493365 No free full text.

Abstract: Suppressor of cytokine signaling (SOCS) is a new family of proteins produced in cells. It may play an important role in classic negative feedback loop to regulate cytokine signal transduction. SOCS-1 was observed and confirmed firstly. Expression of SOCS-1 can inhibit cytokine signal transduction of some cytokines, such as IL-6, LIF, OSM, INF-gamma, GH, and so on, many immune responses are regulated by them in vivo. Abnormal expression of SOCS-1 is closely related to some human diseases. It plays an important role in the development of leukemia, rheumatoid arthritis, liver cirrhosis and liver cancer. In this review, the advances of research on the relationship between SOCS-1 and cytokine, and its correlation with some diseases were summarized.

Lu LJ, Bao CD, Dai M, Teng JL, Fan W, Du F, Yang NP, Zhao YH, Chen ZW, Xu JH, He PG, Wu HX, Tao Y, Zhang MJ, Han XH, Li XF, Gu JR, Li JH, Yu H. · Ren Ji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. · Arthritis Rheum. · Pubmed #19565542 No free full text.

Abstract: OBJECTIVE: To assess the efficacy and safety of T-614 versus methotrexate (MTX) in patients with active rheumatoid arthritis (RA). METHODS: In this multicenter, double-blind trial, 489 patients randomly received either T-614 25 mg/day for the first 4 weeks and 50 mg/day for the subsequent 20 weeks (group 1, n = 163), T-614 50 mg/day for 24 weeks (group 2, n = 163), or MTX 10 mg/week for the first 4 weeks and 15 mg/week for the subsequent 20 weeks (n = 163). Clinical and laboratory parameters were analyzed at baseline and at 4, 10, 17, and 24 weeks. RESULTS: After 24 weeks of treatment, the American College of Rheumatology 20% improvement criteria response rate for patients in T-614 group 2 (63.8%) was not statistically significantly different from that for patients receiving MTX treatment (62.0%), and was superior to that for patients in T-614 group 1 (50.9%). The result of the noninferiority analysis indicated that the efficacy of T-614 (50 mg/day) was not lower than that of MTX by <10%. Rheumatoid factor and IgA, IgG, and IgM demonstrated a statistically significant decrease in all groups. Frequently reported adverse events included hematologic disorder, skin reactions, gastrointestinal symptoms, and transient liver enzyme elevations in the T-614 therapy groups. Side effects in the T-614 groups were generally fewer and milder than in the MTX group, except for skin reactions. There were no prominent cardiovascular adverse events and gastrointestinal ulcers found in the T-614 groups. CONCLUSION: Results indicate that T-614 therapy 50 mg/day is effective and well tolerated, and represents a new option for the treatment of patients with active RA.

Du F, Lü LJ, Fu Q, Dai M, Teng JL, Fan W, Chen SL, Ye P, Shen N, Huang XF, Qian J, Bao CD. · Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. · Arthritis Res Ther. · Pubmed #19019215 links to  free full text

Abstract: INTRODUCTION: T-614 is a novel oral antirheumatic agent for the treatment of rheumatoid arthritis. Whether it has immunomodulatory or disease-modifying properties and its mechanism of action are largely undetermined. METHODS: Rats with collagen-induced arthritis (CIA) were treated with T-614 (5 and 20 mg/kg) daily. Animals receiving methotrexate (1 mg/kg every 3 days) and the nonsteroidal anti-inflammatory agent nimesulide (10 mg/kg per day) were used as controls. A combination therapy group was treated with both T-614(10 mg/kg per day) and methotrexate (1 mg/kg every 3 days). Hind paw swelling was evaluated and radiographic scores calculated. Serum cytokine levels were assessed by Bio-plex analysis. Quantitative PCR was used to evaluate expression of mRNA for interferon-gamma, IL-4 and IL-17. Serum IL-17 and anti-type II collagen antibodies (total IgG, IgG1, IgG2a, IgG2b and IgM) were measured using ELISA. RESULTS: Oral T-614 inhibited paw swelling and offered significant protection against arthritis-induced cartilage and bone erosion, comparable to the effects of methotrexate. CIA rats treated with T-614 exhibited decreases in both mRNA expression of IL-17 in peripheral blood mononuclear cells and lymph node cells, and circulating IL-17 in a dose-dependent manner. T-614 also reduced serum levels of tumor necrosis factor-alpha, IL-1beta and IL-6. A synergistic effect was observed for the combination of methotrexate and T-614. In addition, T-614 (20 mg/kg per day) depressed production of anti-type II collagen antibodies and differentially affected levels of IgG2a subclasses in vivo, whereas IgM level was decreased without any change in the IgG1 level. Together, the findings presented here indicate that the novel agent T-614 has disease-modifying effects against experimental arthritis, as opposed to nimesulide. CONCLUSIONS: Our data suggested that T-614 is an effective disease-modifying agent that can prevent bone/cartilage destruction and inflammation in in CIA rats. Combination with methotrexate markedly enhances the therapeutic effect of T-614.

Li H, Dai M, Zhuang Y. · Institute of Developmental Biology and Molecular Medicine, Fudan University, Shanghai 200433, China. · Immunity. · Pubmed #15485632 links to  free full text

Abstract: Sjogren's syndrome is an autoimmune disease with clinical hallmarks of keratoconjunctivitis sicca (dry eyes) and xerostomia (dry mouth). The genetic basis of this autoimmune disease is poorly understood. Id3 is an immediate early-response gene in growth regulation and is involved in TCR-mediated T cell selection during T cell development. Here, we show that Id3-deficient mice develop many disease symptoms found in primary Sjogren's syndrome patients including dry eyes and mouth, lymphocyte infiltration in lachrymal and salivary glands, and development of anti-Ro and anti-La antibodies. Adoptive transfer experiment indicated a T cell intrinsic role for Id3 in the development of Sjogren's symptoms. Furthermore, genetic ablation of T cells or neonatal 3 day thymectomy in Id3-deficient mice showed a rescue of disease symptoms, suggesting a thymic origin of autoimmune T cells. Thus, this study establishes a critical connection between Id3-mediated T cell development and autoimmune diseases.