课件：吕良敬系统性红斑狼疮诊治进展江苏.ppt

减少IL-2的转录，抑制T细胞的活化 * LN的发病机理：首先，树突状细胞吞噬了一系列包括病毒、凋亡细胞，激活了炎症反应。启动了T细胞、B细胞，产生自身抗体，导致自身免疫反应的发生，必威体育精装版的研究报告认为肾小球正常的调亡、细胞异常的调亡或调亡细胞清除障碍可以引起原位免疫反应。 树突状细胞是体内最强的抗原呈递细胞,能刺激和致敏幼稚T细胞,在发动初次免疫应答中具有重要的作用 新型小分子免疫调节剂艾拉莫德（艾得辛）可有效减轻狼疮小鼠的肾脏损伤和狼疮症状 * 艾拉莫德可通过非抗增殖的方式有效抑制体外人B细胞分化为浆细胞。 (A)艾拉莫德结构式。 (B)正常人外周血CD19+细胞经磁珠阴选后在IL2+IL21+IL4+CD40L联合刺激下体外培养。Day7培养细胞中CD27+CD38+CD19-浆细胞比例。 (C)艾拉莫德对正常人B细胞细胞凋亡及增殖影响不明显。Day3采用BrdU/7-AAD流式分析细胞周期。艾拉莫德使B细胞更多停留于G0-G1期而较少进入M-G2期，但结果无统计学差异；而两组的凋亡细胞比例则几乎没有差异。 (D)艾拉莫德可调节浆细胞分化的关键转录因子格局。正常人外周血CD19+细胞体外培养，Day4流式检测核内转录因子表达。艾拉莫德抑制Blimp-1、XBP1而上调PAX5，对IRF4无明显影响。 * 艾拉莫德可改善MRL/lpr免疫性肾炎。雌性MRL/lpr小鼠，自第8周龄起给予艾拉莫德 30mg/kg·d（n=14）或空白载体溶液（n=16）。 (A) 小鼠蛋白尿水平。 (B) 第28周处死所有小鼠观察肾脏病理。艾拉莫德治疗后小鼠肾组织，大致正常；安慰剂组小鼠肾脏，可见新月体、小球硬化（星号）、间质炎症细胞浸润及管型等多种病变。 （C）小鼠肾脏病理评分 (D)MRL/lpr小鼠，自第8周龄起给予艾拉莫德30mg/kg·d或空白载体溶液。艾拉莫德可降低小鼠血清抗dsDNA抗体滴度。 (E)艾拉莫德在给药12w后可显著降低MRL/lpr小鼠血清各亚型免疫球蛋白水平，与阳性对照药物环磷酰胺（Cyc）作用接近。 ? * Abstract Objective To assess the efficacy and safety of subcutaneous (SC) belimumab in patients with systemic lupus erythematosus (SLE). Methods Patients with moderate-to-severe SLE (SELENA-SLEDAI ≥8) were randomized (2:1) to weekly belimumab 200 mg SC or placebo by prefilled syringe, plus standard SLE therapy (SoC), for 52 weeks. Primary endpoint was SLE Responder Index (SRI4) at Week 52. Secondary endpoints were time to severe flare and reduction in corticosteroid dose. Safety was assessed by adverse event (AE) reporting and laboratory testing. Results Of 839 patients randomized, 836 (556 belimumab/280 placebo) received treatment; 159 withdrew. At entry, mean SELENA-SLEDAI scores were 10.5 (belimumab) and 10.3 (placebo). More patients who received belimumab were SRI4 responders than those who received placebo (61.4% vs 48.4%; odds ratio [OR] [95% CI]: 1.68 [1.25, 2.25]; p=0.0006). In the belimumab group, time to and risk of severe flare were improved (median 171.0 versus 118.0 days; HR [95% CI]: 0.51 [0.35, 0.74]; p=0.0004), and more patients reduced corticosteroid dose by ≥25% to ≤7.5 mg/d