自身免疫性炎症综合症.ppt

Autoinflammatory Syndrome,1,2,3,Autoinflammatory - 1999,“ The autosomal dominant periodic fevers therefore represent a class of human disease shown to be caused by mutations in TNF receptors. Autoantibodies are not a general feature of these illnesses or the recessively inherited FMF, and for this reason the term autoinflammatory is preferable to autoimmune in describing these disorders. ” “Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes.” McDermott, et al., Cell. 1999 Apr 2;97(1):133-44.,4,“Autoinflammatory” Disease,At the time, autoinflammatory was coined to distinguish diseases involving innate immune dysregulation (FMF & TRAPS) from autoimmune diseases known to involve adaptive immune dysregulation (SLE & RA). Two premises of autoimmune disease are unfulfilled in autoinflammatory disorders: The inflammation is seemingly “unprovoked”. Autoantibodies and antigen-specific T cells are absent.,5,6,7,8,9,AID IL-1 Pathway,Goldbach-Monsky, Clin Exp Immunol, 2011, 167:391-404,10,Pro-IL-1b,IL-1b,Inactive,active,NLRP3 and IL-1,Schroder and Tschopp, Cell, 2010, 140:821-823,11,Goldbach-Mansky, Clin Exp Immunol, 2012, 167:391-404,Activation of Inflammasome,12,13,编码不同蛋白的基因突变,14,AID other Cytokine Pathways,Goldbach-Monsky, Clin Exp Immunol, 2011, 167:391-404,15,隐热蛋白相关周期综合征,16,17,Cryopyrin相关周期综合征（CAPS）,18,19,CAPS临床分型和疾病谱,轻度表型,中度表型,重度表型,FCAS 寒冷诱发的荨麻疹 发热 关节痛,MWS 荨麻疹 低热 关节炎 淀粉样变 耳聋,NOMID 新生儿起病的荨麻疹 发热 关节病，可变形 淀粉样变 中枢神经系统表现 脑膜炎 视力障碍,20,21,22,23,24,25,26,27,IL-1阻滞剂治疗CAPS,28,29,家族性地中海热（FMF）,30,2019/10/26,31,32,治疗： NSAIDs： 秋水仙碱：减缓WBC趋化和炎性因子产生，预防淀粉样变神经病变 IL-1拮抗剂 预后： 1个基因突变：治疗反应良好 H478Y MEFV variant：秋水仙碱无效 M694V突变：易淀粉样变,33,激素有效（3-5天），秋水仙碱无效 TNFa拮抗剂和IL-1拮抗剂部分有效,34,MKD（高IgD综合征，HIDS）,35,36,37,38,肿瘤坏死因子受体相关周期综合征（TRAPS）,39,40,41,PAPA综合征,42,43,44,45,46,47,48,Schnitzlers syndrome,49,50,51,Schnitzler Syndrome,Differential Diagnosis,52,NOD2 Associated Autoinflammatory Diseases,NOD2 gene: R