自体免疫疾病（优质课件）.ppt

自体免疫疾病 器官特异性 非器官特异性 自体免疫疾病 肌肉 肾脏 皮肤 关节 PathologicalFactorsinRheumaticDisorders Rheumaticdiseasesaremultisystemdisorderscausedbytissuedamageresultingfromautoantibodies cytotoxicTlymphocytes complement fixingimmunecomplexdeposition andinflammatorymediators InflammatoryParameters ESRAcutephasereactantsImmunoglobulinsComplementcomponentsInflammatorymediators cytokines prostanoids ESRaredeterminedbythethreeforces Surfacefreeenergy VandeWaal sforce cohesiveforceElectricalchargeassociatedwithRBC repulsiveforceDielectricconstantofthemedium dissipatestheforce CalculationEquationforESR Vs 2 9x Ps PL R2 nxgVs thelimitingvelocityofthesphereR theradiusofthespherePsandPL thedensitiesofthesphereandoftheliquidg theaccelerationduetogravityn theviscosityoftheliquid SerumProteinsandDrugsThatAffecttheESRRate AcutePhaseReactants TheAcutePhaseResponseFollowsCellInjuryandTissueDamageCausedby Acuteinfections i e bacterialorparasiticTrauma i e blunt surgery andburnsIschemicnecrosis i e acutemyocardialinfarctionMalignantdisease I e tumorgrowthandmetastasisConnectivetissuedisease i e rheumatoidarthritis rheumaticfeverandothersAcuteabdominalinflammation i e cholecystitisandpancreatitisVaccination I e typhoid FunctionalPropertiesofHumanAcutePhaseProteins C ReactiveProtein CRP Normalplasmaprotein concentrationfrom0 068 8 8mg mlAcutephasereactant concentrationupto500mg mlSynthesizedbyhepatocytesMolecularweight105 500daltonsFiveidenticalnon glycosylated non covalentlyassociatedsubunitsAminoacidsequencehomologouswithserumamyloidAcomponent SAA RheumaticDiseaseinWhichElevatedC ReactiveProteinLevelsmayOccur cACR 类风湿性关节炎 RA 类风湿性关节炎 RA 类风湿性关节炎是一种重要的自体免疫疾病 可导致关节破坏变形 骨骼变化以及全身性的病变 类风湿性关节炎的骨骼变化包括发炎关节旁的骨缺乏 软骨侵蚀 类风湿性关节炎是一种全身性的变化 患者不但关节疼痛 可能关节会逐渐变形 过去十年来 类风湿关节炎在冶疗上的改变有着明显的进步 我们不再视其为一仅局限于关节的慢性病变 反之 却视为一甚富侵略性的全身性疾患 RheumatoidArthritis RA Achronic systemic autoimmune inflammatorydiseaseofunknownetiologyCharacterizedbypersistentintenseimmunologicalactivityinflammatoryanderosivesynovitis usuallyinvolvingperipheraljointinasymmetricfashionlocaldestructionofboneandcartilageavarietyofsystemicmanifestation Themostcommoninflammatoryjointdisease NormalSynovium RheumatoidSynovium cACR cArthritis RheumatismFoundation PageNo 20 52 ClinicalfeaturesofRheumatoidArthritisinthehand Early WastingsmallmusclesExtensortendonsheathswellingFusiformswellingofPIPjointsMCPjointsynovitiswithswelling Late DeformityUlnardeviationSwan neckdeformitySubluxationofMCPJ 2 Lossoffunction 类风湿性关节炎 RA Rheumatoidarthritis 类风湿性关节炎 RA 类风湿性关节炎 RA 类风湿关节炎的早期关节破坏 类风湿性关节炎的临床病程 变异性极大只有小于1 5的病人在发病10 12年内没有出现关节破坏或变形在发病头六年内关节破坏进展最快 1st 2nd 3rd 在发病头两年内对于关节功能的影响最显着 MarkersofseverediseaseactivityinRA 1 Generalpolyarthritisinvolvingbothsmallandlargejoints2 Extra articulardisease especiallynodulesandvasculitis3 PersistentlyelevatedESRorCRPwithactivesynovitis4 RF positivewithhightitier5 Radiologicallyerosionswithintwoyearsofdiseaseonset6 HLA DR4positive Majorextra articularfeaturesofRA Common AnemiaLymphadenopathyRheumatoidnodulesMusclewastingEpiscleritisandkeratoconjuntivitisPeripheralsensorypolyneuropathy Uncommon PleuraleffusionPulmonaryfibrosisPericardialeffusionSystemicvasculitisSplenomegaly RheumatoidFactors AnautoantibodyreactivewithdenaturedhumanorrabbitIgGGenerationofRFsinthefollowingconditions Autoimmunedisorders RA SLE Sjogren ssyndrome vasculitisChronicinflammationChronicinfectionMalignancyaging SomeDiseaseCommonlyAssociatedwithRheumatoidFactor FalsePositiveRheumatoidFactorTest Sarcoidosis10 Syphilis10 Hepatitis25 Viralinfection15 Leprosy25 Subacutebacterialendocarditis50 Oldage 65y o 35 BiomarkersinRheumatoidArthritis RheumatoidfactorAnti CCP anti cycliccitrullinatedpeptides AbThepresenceofanti CCPAbisthemostaccuratebiomarkerforRAinbothselectedandunselectedcohorts GoalsofRAManagement PainreliefandinflammationreductionActivitiesofdailylivingandqualityoflifeLongtermjointdamagecontrolorpreventionDiseaseprocessinterruptionormodificationTherapyrelatedsideeffectsavoidance 僵直性脊椎关节炎 AS 全身红斑性狼疮 好发于20 40岁之年轻女性女性与男性之比例约为10 1侵犯多个器官系统 临床表现千变万化难以捉摸 全身红斑性狼疮 全身红斑性狼疮 全身红斑性狼疮与自体抗体 患者体内常出现许多自体抗体最常出现之自体抗体为抗核抗体 ANA 自体抗体为造成导致器官伤害的重要原因有些自体抗体为追踪病情之重要指针 AntinuclearAntibody ANA Disease SpecificAutoantibodies OrganspecificautoantibodiesAutoantibodiesforsystemicautoimmunedisoedersAutoantibodiesinsystemiclupuserythematosus 器官特异性自体免疫疾病对应抗原的种类 自体免疫抗体与全身性自体免疫疾病之相关 ListofAutoantibodiesReportedinSLE 全身红斑性狼疮 常见慢性并发症 1 肾炎及肾脏衰竭 2 中枢神经病变 3 感染症 4 贫血及血小板降低 全身红斑性狼疮的活动性与复发 活动性 SLEactivity 复发 flareup 常见症状 发烧 关节炎 水肿加重 红斑 癫痫发作 呼吸困难 起伏不定 难以捉摸 影响全身红斑性狼疮复发的因素 阳光曝晒紫外线 怀孕 压力与情绪 感染 全身红斑性狼疮活动性的追踪 1 抗DNA抗体 2 补体C3 C4 3 发炎指针 血球及肾功能 免疫学检查与全身红斑性狼疮活动性 临床症状 临床前期之复发 Algorithmfortheuseofantinuclearantibodies ANAs inthediagnosisofconnectivetissuedisorders Anti NeutrophilCytoplasmicAntibodies ANCA cANCA anti proteinase