自体免疫疾病课件

自体免疫疾病自体免疫疾病1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2自体免疫疾病课件3自体免疫疾病课件4自体免疫疾病课件5自体免疫疾病课件6PathologicalFactorsinRheumaticDisorders

Rheumaticdiseasesaremultisystemdisorderscausedbytissuedamageresultingfromautoantibodies,cytotoxicTlymphocytes,complement-fixingimmunecomplexdeposition,andinflammatorymediatorsPathologicalFactorsinRheuma7InflammatoryParametersESRAcutephasereactantsImmunoglobulinsComplementcomponentsInflammatorymediators:cytokines,prostanoidsInflammatoryParametersESR8

ESRaredeterminedbythethreeforcesSurfacefreeenergy(VandeWaal＇sforce):cohesiveforceElectricalchargeassociatedwithRBC:repulsiveforceDielectricconstantofthemedium:dissipatestheforceESRaredeterminedbythet9CalculationEquationforESR

Vs=2/9x(Ps-PL)R2/nxgVs=thelimitingvelocityofthesphereR=theradiusofthespherePsandPL=thedensitiesofthesphereandoftheliquidg=theaccelerationduetogravityn=theviscosityoftheliquidCalculationEquationforESR10SerumProteinsandDrugsThatAffecttheESRRateESRincreaseESRdecrease

Fibrinogen

ACTH

Immunoglobulins

Cortisone

Dextran

Ethambutol

Methyldopa

Quinine

Procainamide

Salicylate

Oralcontraceptives

Penicillamine

Methylsergide

Theophylline

Trifluperidol

VitamineASerumProteinsandDrugsThat11AcutePhaseReactantsTheAcutePhaseResponseFollowsCellInjuryandTissueDamageCausedby:Acuteinfections:i.e.,bacterialorparasiticTrauma:i.e.,blunt,surgery,andburnsIschemicnecrosis:i.e.,acutemyocardialinfarctionMalignantdisease:I.e.,tumorgrowthandmetastasisConnectivetissuedisease:i.e.,rheumatoidarthritis,rheumaticfeverandothersAcuteabdominalinflammation:i.e.cholecystitisandpancreatitisVaccination:I.e.,typhoidAcutePhaseReactantsTheAcute12FunctionalPropertiesofHumanAcutePhaseProteinsFunctionalGroupProteinFunctionHostdefenseproteinsC-reactiveprotein(CRP)Complementactivation,opsonicationMannan-bindingprotein(MBP)Complementactivation,opsonizationComplementproteinsC3,C4,C5FactorB,C9FactorH,C4bpIncreasedvascularpermeability,opsonization,bacterialkillingFibrinogenFormationofhemostaticplugs,woundhealingProteinaseinhibitors

1-Proteinaseinhibitor(1-PI)Controlofextracellularmatrixdegradation

1-Antichymotrypsin(1-Achy)Controlofextracellularmatrixdegradation

2-Antiplasmin(2-AP)ControlofplasminC1inhibitor(C1INH)ControlofcomplementandcontacesystemactivationAntioxidantsCeruloplaasminInhibitionofoxyradicalformationHemopexin(Hx)Bindingofheme,inhibitionoflipidperoxidationHaptoglobulin(HP)Bindingofhemoglobulin,inhibitionoflipidperoxidationFunctionunknownSerumamyloidA(SAA)

1-AcidglycoproteinFunctionalPropertiesofHuman13C-ReactiveProtein(CRP)Normalplasmaprotein,concentrationfrom0.068--8.8mg/mlAcutephasereactant,concentrationupto500mg/mlSynthesizedbyhepatocytesMolecularweight105,500daltonsFiveidenticalnon-glycosylated,non-covalentlyassociatedsubunitsAminoacidsequencehomologouswithserumamyloidAcomponent(SAA)C-ReactiveProtein(CRP)Normal14RheumaticDiseaseinWhichElevatedC-ReactiveProteinLevelsmayOccurGoutRheumatoidarthritisJuvenilerheumatoidarthritisPsoriaticarthritisAnkylosingspondylitisReiter＇ssyndromePolymyalgiarheumatica-giantcellarteritisSystemicvasculitisWegener＇sgranulomatosisBehcet＇ssyndromeSystemiclupuserythematosusRheumaticDiseaseinWhichEle15cACR类风湿性关节炎(RA)cACR类风湿性关节炎(RA)16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。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17RheumatoidArthritis(RA)Achronic,systemic,autoimmune,inflammatorydiseaseofunknownetiologyCharacterizedbypersistentintenseimmunologicalactivityinflammatoryanderosivesynovitis,usuallyinvolvingperipheraljointinasymmetricfashionlocaldestructionofboneandcartilageavarietyofsystemicmanifestation.ThemostcommoninflammatoryjointdiseaseRheumatoidArthritis(RA)18自体免疫疾病课件19NormalSynoviumRheumatoidSynoviumcACRcArthritis&RheumatismFoundationPageNo.20/52NormalSynoviumRheumatoidSyno20自体免疫疾病课件21ClinicalfeaturesofRheumatoidArthritisinthehandEarlyWastingsmallmusclesExtensortendonsheathswellingFusiformswellingofPIPjointsMCPjointsynovitiswithswellingLateDeformityUlnardeviationSwan-neckdeformitySubluxationofMCPJ2.LossoffunctionClinicalfeaturesofRheumatoi22类风湿性关节炎(RA)类风湿性关节炎(RA)23RheumatoidarthritisRheumatoidarthritis24类风湿性关节炎(RA)类风湿性关节炎(RA)25类风湿性关节炎(RA)类风湿性关节炎(RA)26自体免疫疾病课件27类风湿关节炎的早期关节破坏类风湿关节炎的早期关节破坏28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类风湿性关节炎的临床病程变异性极大29MarkersofseverediseaseactivityinRA1.Generalpolyarthritisinvolvingbothsmallandlarge joints2.Extra-articulardisease,especiallynodulesandvasculitis3.PersistentlyelevatedESRorCRPwithactivesynovitis4.RF-positivewithhightitier5.Radiologicallyerosionswithintwoyearsofdiseaseonset6.HLA-DR4positiveMarkersofseverediseaseacti30Majorextra-articularfeaturesofRACommonAnemiaLymphadenopathyRheumatoidnodulesMusclewastingEpiscleritisandkeratoconjuntivitisPeripheralsensorypolyneuropathyUncommonPleuraleffusionPulmonaryfibrosisPericardialeffusionSystemicvasculitisSplenomegalyMajorextra-articularfeatures31RheumatoidFactorsAnautoantibodyreactivewithdenaturedhumanorrabbitIgGGenerationofRFsinthefollowingconditions:Autoimmunedisorders:RA,SLE,Sjogren＇ssyndrome,vasculitisChronicinflammationChronicinfectionMalignancyagingRheumatoidFactorsAnautoantib32SomeDiseaseCommonlyAssociatedwithRheumatoidFactorRheumaticDiseases

Filariasis

RheumatoidarthritisChronicBacterialinfections

Systemiclupuserythematosus

Tuberculosis

Scleroderma

Leprosy

Mixedconnectivetissuedisease

Yaws

Sjogren＇ssyndrome

SyphilisViralInfections

Brucellosis

Acquiredimmunodeficiencysyndromes

Subacutebacterialendocarditis

Mononucleosis

salmonellosis

HepatitisNeoplasms

Influenza

Tumorsafterradiationtherapyorchemotherapy

Aftervaccination(mayyieldfalselyelevatedOtherHyperglobulinemicStates

titersofantivivalantibodies)

HypergammaglobulinemicpurpuraParasiticInfections

Cryoglobulinemia

Trypanosomiasis

Chronicliverdisease

Kala-azar

Sarcoid

Malaria

Otherchronicpulmonarydiseases

SchistosomiasisSomeDiseaseCommonlyAssociat33FalsePositiveRheumatoidFactorTestSarcoidosis10%Syphilis10%Hepatitis25%Viralinfection15%Leprosy25%Subacutebacterialendocarditis50%Oldage(>65y/o)35%FalsePositiveRheumatoidFact34BiomarkersinRheumatoidArthritisRheumatoidfactorAnti-CCP(anti-cycliccitrullinatedpeptides)AbThepresenceofanti-CCPAbisthemostaccuratebiomarkerforRAinbothselectedandunselectedcohortsBiomarkersinRheumatoidArthr35GoalsofRAManagementPainreliefandinflammationreductionActivitiesofdailylivingandqualityoflifeLongtermjointdamagecontrolorpreventionDiseaseprocessinterruptionormodificationTherapyrelatedsideeffectsavoidanceGoalsofRAManagementPainrel36僵直性脊椎关节炎(AS)僵直性脊椎关节炎(AS)37自体免疫疾病课件38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好发于20-40岁之年轻女性39全身红斑性狼疮全身红斑性狼疮40全身红斑性狼疮全身红斑性狼疮41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42自体免疫疾病课件43自体免疫疾病课件44AntinuclearAntibody(ANA)DiseaseDiseasePatientswithANAs(%)Systemiclupuserythematosus99Drug-inducedlupus100Systemicsclerosis97Mixedconnectivetissuedisease93Polymyositisanddermatomyositis78Sjogren＇ssyndrome96AntinuclearAntibody(ANA)Dis45SpecificAutoantibodiesOrganspecificautoantibodiesAutoantibodiesforsystemicautoimmunedisoedersAutoantibodiesinsystemiclupuserythematosusSpecificAutoantibodiesOrgans46器官特异性自体免疫疾病对应抗原的种类疾病自体抗原桥本氏甲状腺炎(Hashimoto＇sthyroiditis)Thyroidperoxidase(microsomalantigen)ThyroglobulinThyroid-stimulatingimmunoglobulin葛雷氏病(Grave＇sdisease)ThyroidperoxidaseThyroglobulinThyroid-stimulatingimmunoglobulin(TSI)Thyroidgrowth-stimulatingikmmunoglobulin(TGSI)Thyrotropinbinding-inhibitoryimmunoglobulin(TBII)第一型糖尿病Insulin,insulinreceptors,isletcells胰岛素抗性糖尿病Insulin,insulinreceptors爱迪生病(Addison＇sdisease)Adrenalcortex恶性贫血(Perniciousanemia)Intrinsicfactor,parietalcells重症肌无力Acetycholinereceptors多发性硬化症(Multiplesclerosis)MyelinbasicproteinGoodpasture＇s病Basementmembrane(lungandglomeruli)寻常性天疱疮(pemphigusvulgaris)Intracellularcement水泡性类天疱疮(Bullouspemphigoid)Basementmembrane(skin)非分节性白斑症(Non-segmentalvitiligo)Membraneproteinsonkeratinocyteandmelanocyte器官特异性自体免疫疾病对应抗原的种类疾47自体免疫抗体与全身性自体免疫疾病之相关自体免疫抗体相关之疾病Anti-dsDNASLEAnti-SmSLEAnti-laminSLEAnti-histoneSLE,Drug-inducedlupusAnti-U1RNPSLE,MCTDAnti-SSA/RoSLE,Sjogren＇ssyndromeAnti-SSB/LaSLE,Sjogren＇ssyndromeAnti-PCNA/cyclinSLEAnti-ribosomalPNP-SLEAnti-Scl-70/topoisomeraseISclerodermaAnti-KuSLE,sclerodermaAnti-centromere/kinetochoreCRESTAnti-RNApolymeraseISclerodermaAnti-PM-SclSclerodermaAnti-Jo-1(tRNAsynthetase)PolymyositisAnti-cardiolipinAnti-phospholipidsydnromeAnti-neutrophilcytoplasmicantigenWegener＇sgranulomatosis,othervasculitis自体免疫抗体与全身性自体免疫疾病之相关自体免疫抗体相关之疾病48ListofAutoantibodiesReportedinSLEAgainst:1.ANA17.PCNA/Cyclin33.Ribosomal-P47.Poly(ADPribose)2.SsDNA18.HTLV-134.Canephriticfactor,48.Poly(A)polymerase3.DsDNA19.HIV-gp120

C3convertaseC1q49.ProteinkinaseNII4.Z-DNA20.Mycobacteria35.Antiendothelial50.Prothymosin5.PolyI21.Laminin36.Fibronectin51.ReplicationproteinA6.PolyG22.Heatshockprotein(90kD)37.Golgiapparatus52.Sp1007.Poly(dt)23.Klebsiella38.Mitoticspindleapparatus53.RA-338.Histones24.Vimentin39.Mi/Ma/Mc54.Nucleosomes9.Cardiolipin25.Heparansulfate40.AnnexinXI55.Ubiquitine10.ENA26.LAC/FacII,VIII,XII)41.DNApolymerase,56.Glycosaminoglycans11.RNP/hnRNP27.Lymphocytes(LCTA,Ts,NK)

-RNApolymeraseI-III57.Lipocortin-112.Sm28.Erythrocytes(Coombs＇)42.HMG-1,2,1758.Pyruvatedehydrogenase13.SS-A/Ro29.Platelets43.L759.Anti-Pribosomalprotein14.SS-B/La30.Leukocytes44.Nuclearhelicase15.RNA31.Neuronal45.Nucleosides16.Ku/Ki(SL)32.Glycolipids46.C-mycListofAutoantibodiesReporte49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常见慢性并发症1.肾炎及肾脏衰竭2.中枢50自体免疫疾病课件51全身红斑性狼疮的活动性与复发活动性(SLEactivity)