自身免疫性炎症综合症PPT课件.ppt

AutoinflammatorySyndrome,1,2,3,Autoinflammatory-1999,“TheautosomaldominantperiodicfeversthereforerepresentaclassofhumandiseaseshowntobecausedbymutationsinTNFreceptors.AutoantibodiesarenotageneralfeatureoftheseillnessesortherecessivelyinheritedFMF,andforthisreasonthetermautoinflammatoryispreferabletoautoimmuneindescribingthesedisorders.”“Germlinemutationsintheextracellulardomainsofthe55kDaTNFreceptor,TNFR1,defineafamilyofdominantlyinheritedautoinflammatorysyndromes.”McDermott,etal.,Cell.1999Apr2;97(1):133-44.,4,“Autoinflammatory”Disease,Atthetime,autoinflammatorywascoinedtodistinguishdiseasesinvolvinginnateimmunedysregulation(FMF&TRAPS)fromautoimmunediseasesknowntoinvolveadaptiveimmunedysregulation(SLE&RA).Twopremisesofautoimmunediseaseareunfulfilledinautoinflammatorydisorders:Theinflammationisseemingly“unprovoked”.Autoantibodiesandantigen-specificTcellsareabsent.,5,6,7,8,9,AIDIL-1Pathway,Goldbach-Monsky,ClinExpImmunol,2011,167:391-404,10,Pro-IL-1b,IL-1b,Inactive,active,NLRP3andIL-1,SchroderandTschopp,Cell,2010,140:821-823,11,Goldbach-Mansky,ClinExpImmunol,2012,167:391-404,ActivationofInflammasome,12,13,编码不同蛋白的基因突变,14,AIDotherCytokinePathways,Goldbach-Monsky,ClinExpImmunol,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）,30,31,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H478YMEFVvariant：秋水仙碱无效M694V突变：易淀粉样变,32,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,33,MKD（高IgD综合征，HIDS）,34,35,36,37,肿瘤坏死因子受体相关周期综合征（TRAPS）,38,39,40,PAPA综合征,41,42,43,44,45,46,47,Schnitzlerssyndrome,48,49,50,SchnitzlerSyndrome,DifferentialDiagnosis,51,NOD2AssociatedAutoinflammatoryDiseases,NOD2gene:R70