自身免疫性炎症综合症课件

AutoinflammatorySyndrome

Autoinflammatory-1999“…Theautosomaldominant

periodicfevers

thereforerepresentaclassof

human

diseaseshowntobecausedbymutationsin

TNF

receptors.Autoantibodiesarenotageneralfeatureoftheseillnessesortherecessivelyinherited

FMF,andforthisreasontheterm

autoinflammatory

ispreferabletoautoimmune

indescribingthesedisorders.

”“Germlinemutationsintheextracellulardomainsofthe55kDaTNFreceptor,TNFR1,defineafamilyofdominantlyinheritedautoinflammatorysyndromes.”

McDermott,etal.,Cell.

1999Apr2;97(1):133-44.“Autoinflammatory”DiseaseAtthetime,autoinflammatorywascoinedtodistinguishdiseasesinvolvinginnateimmunedysregulation(FMF&TRAPS)fromautoimmunediseasesknowntoinvolveadaptiveimmunedysregulation(SLE&RA).Twopremisesofautoimmunediseaseareunfulfilledinautoinflammatorydisorders:Theinflammationisseemingly“unprovoked”.Autoantibodiesandantigen-specificTcellsareabsent.AID–IL-1PathwayGoldbach-Monsky,ClinExpImmunol,2011,167:391-404Pro-IL-1bIL-1bInactiveactiveNLRP3andIL-1SchroderandTschopp,Cell,2010,140:821-823Goldbach-Mansky,ClinExpImmunol,2012,167:391-404ActivationofInflammasome编码不同蛋白的基因突变AID–otherCytokinePathwaysGoldbach-Monsky,ClinExpImmunol,2011,167:391-404隐热蛋白相关周期综合征Cryopyrin相关周期综合征（CAPS）炎性刺激含有cryopyrin的炎症小体活化（CAPS）半胱天东酶1活化（IL-1β转化酶）产生IL-1β炎症免疫细胞活化凋亡和组织损伤炎症小体pyrin类异戊二烯代谢突变cryopyrin作用：尚未完全阐明降低炎症活化的阈值，使炎症触发更加敏感炎症的启动正常，但炎症的关闭被干扰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NLRP3炎性体基因突变IL-1阻滞剂治疗CAPS炎性刺激含有隐热蛋白的炎症小体活化半胱天东酶1活化（IL-1β转化酶）产生IL-1β炎症免疫细胞活化组织损伤炎症小体IL-1阻滞剂

Anakinra：IL-1ra拮抗剂

Canakinumab：IL-1β单抗

Rilonacept：IL-1Trap家族性地中海热（FMF）含有cryopyrin的炎症小体活化炎性刺激半胱天东酶1活化（IL-1β转化酶）产生IL-1β炎症免疫细胞活化凋亡和组织损伤pyrin（FMF）炎症小体治疗：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）炎性刺激含有cryopyrin的炎症小体活化（CAPS）半胱天东酶1活化（IL-1β转化酶）产生IL-1β炎症免疫细胞活化凋亡和组织损伤炎症小体pyrin类异戊二烯代谢MVK(甲羟戊酸激酶)（HIDS）肿瘤坏死因子受体相关周期综合征（TRAPS）PAPA综合征炎性刺激含有cryopyrin的炎症小体活化半胱天东酶1活化（IL-1β转化酶）产生IL-1β炎症免疫细胞活化凋亡和组织损伤炎症小体pyrin类异戊二烯代谢PSPSTPIP1(PAPA)Schnitzler’ssyndrome

~200casesreportedworldwidedeKoningetal,2007,SeminArthritisRheumSchnitzlerSyndromeDiffere