1、Autoinflammatory Syndrome,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
2、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.,“Autoinflam
3、matory” 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: Th
4、e inflammation is seemingly “unprovoked”. Autoantibodies and antigen-specific T cells are absent.,AID IL-1 Pathway,Goldbach-Monsky, Clin Exp Immunol, 2011, 167:391-404,Pro-IL-1b,IL-1b,Inactive,active,NLRP3 and IL-1,Schroder and Tschopp, Cell, 2010, 140:821-823,Goldbach-Mansky, Clin Exp Immunol, 2012
5、, 167:391-404,Activation of Inflammasome,编码不同蛋白的基因突变,AID other Cytokine Pathways,Goldbach-Monsky, Clin Exp Immunol, 2011, 167:391-404,隐热蛋白相关周期综合征,Cryopyrin相关周期综合征（CAPS）,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,IL-1阻滞剂治疗CAPS,家族性地中海热（
6、FMF）,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,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,MKD（高IgD综合征，HIDS）,肿瘤坏死因子受体相关周期综合征（TRAPS）,PAPA综合征,Schnitzlers syndrome,Schnitzler Syndrome,Differential Diagnosis,NOD2 Associated Autoinflammatory Diseases,NOD2 gene: R702W and IVS8 +158,Yao et al, 2013, J Am Acad Dermatol, 68:624-31,
