类风湿性关节炎的基础研究与进展.ppt

CIA大鼠的骨保护作用-MRI Refer：Fang Du,liang-jing Lv,et al. T-614,a novel immunomodulator,attenuates inflammation and articular damage in collagen induced arthritis. Arthritis Research Therapy 2008,10:R136 a: normal rats; b: CIA rats treated with vehicle; c: CIA rats treated with MTX; d:CIA rats treated with nimesulide e/f: CIA rats treated with T614; g: CIA rats treated with T-614 and MTX a b c d e f g soft tissue swelling (yellow arrow) and localization of bone marrow edema (yellow triangle) MRI检测结果：艾得辛能够几乎完全抑制CIA的炎症和骨髓内水肿。 影像学评估 –X线和CT T-614 offered significant protection against joint damage a b c d e f g A Naive Vehicle MTX nimesulide T614 (5) T614 (20) MTX+T614(10) a b c d e f g C X线平片和CT检测结果显示：艾得辛还能够显著抑制骨吸收和关节破坏。 目录 病因 ---基因因素 ---环境因素 病机 ---RA滑膜炎 ---RA骨侵蚀 基础研究引导治疗的发展 基础研究引导RA的靶向治疗 T cell APCs B cell or macrophage Synoviocytes Pannus Articular cartilage Chondrocytes HLA -DR Production of collagenase and other neutral proteases Abs Immune complexes Articular cartilage Production of collagenase and other neutral proteases T cell APCs Macrophage B cell B cell cytokines Osteoclast Complements TNF-? IL-1 IL-6 RA治疗方法的递进 Drugs Objectives Concepts 1980s MTX, D-PA, Gold... Signs symptoms pyramid 1990s DMARDs ? joint damage Combination Leflunomide 2000 Bi-DMARDs Prevent joint damage Early treatment Stop joint damage Tight control 2008 Remission Early intensive ttt 靶向治疗使RA的治疗目标更高 Target Name Function Anti-TNF Etanercept Soluable TNF receptor Infiximab Chimeric anti-TNF Mab Adalimumab Fully human anti-TNF Mab Golimumab Fully human anti-TNF Mab Certolizumab Pegol Pegylated Fab fragment of a humanized MoAb against TNF Anti-IL-1 anakinra IL-1ra Rilonacept Dimeric fusion protein: extracellular IL-1R IgG1-Fc Anti-IL-6 Tocilizumab Humanized anti-human IL-6 receptor antibody Ustekinumab MoAb against receptor (p40) of IL-12 IL-23, Effective for PsA (phase III) B cells Rituximab anti-CD20 monoclonal antibody that selectively dep