自身免疫病英文

Casepresentation RheumatoidArthritis 44yearoldwomanwiththenewonsetofprogressivearthritisoverthepast3months nowunabletowork swelling pain andstiffnessinfingers hands wrists elbows shoulders knees ankles andfeet morningstiffness 8hours fatigueExamrevealsdiffusesymmetricalsynovitisandsubcutaneousnodulesX raysofthehandsshowearlymarginalerosions Autoimmunity AutoimmuneDisease Section1OverviewSection2mechanismofautoimmunediseaseSection3CausesofDamageinAutoimmuneDiseasesSection4ExamplesofautoimmunediseasesSection5Treatmentofautoimmunediseases Section1Overview autoimmunitySpecificadaptiveimmuneresponsesmountedagainstselfantigensautoimmunedisease AID tissuedamageandclinicalsymptomistheresultofautoimmunityauto antibody auto reactiveTcellProduceintheautoimmunityofAntibodyandreactiveTcell canbesingleorganormultisystemdiseasescanbemorethanoneautoantibodyinagivendiseaseloss CausesforLossofself toleranceBypassofhelperT celltolerancemodificationofantigen viadrugs microorganisms expressionofsecondsignalfrommacrophagesstimulatedfrominfectionsMolecularmimicryinfectiousagentsappearsimilartoself antigens streptococcalantigenandmyocardium Polyclonallymphocyteactivationendotoxinscausesuchactivationindependentofspecificantigens Imbalanceofsuppressor helperTcellfunctionanylossofsuppressorT cellfunctionmaycontributetoautoimmunityEmergenceofsequesteredantigensfollowingtraumaorinfection previouslyunseenantigensmayemerge bullouspemphigoidfollowingaburn Theimmunityregulates Organ specificdiseasesSystemicdiseases Section2mechanismofautoimmunedisease 一 Damageproducedbyimmuneattackcanproducealteredformsofselfantigens Somebodysitesareimmunologicallypriviledged Damagetoanimmunologicallyprivilegedsitecaninduceanautoimmuneresponse Severalwaysinwhichinfectiousagentscouldbreakselftolerance 2Damageproducedbyimmuneattackcanproducealteredformsofselfantigens molecularmimicrybycross reactivemicrobialantigencanstimulateautoreactiveBandTcell IncreasedHLAclassIIantigensexpression LimitationsinToleranceMechanismsin Associationofinfectionwithautoimmunedisease Section3CausesofDamageinAutoimmuneDiseases Themostdamageofautoimmunediseasecomefrom Antibody mediateddamageAssociatedwithantibodiestoself proteinscleavedbycytotoxicMononuclearinfiltrateconsistingprimarilyofT cells primarilyCD4 Autoimmunediseasesmediatedbycytotoxicantibodies TypeII Autoimmunediseasesmediatedbyimmunecomplexes TypeIII AutoimmunediseasesmediatedbyT cells TypeIV AutoimmunityinvolvesTcells AbilityofaTcelltorespondisdeterminedbyMHCgenotypeIthasbeenhypothesizedthatsusceptibilitytoanautoimmunediseaseisdeterminedbydifferencesintheabilityofallelicvariantsofMHCmoleculestopresentautoantigenicpeptidesAlternatively selfpeptidesmaydrivethepositiveselectionofdevelopingthymocytesthatarespecificforparticularautoantigens Autoimmunediseasespatientmainauto antibodyofinside anti nucleusantibody ANA anti changesIgGantibody typerheumatismfactor RF anti phospholipidantibody APLantibody anti neutrophilcytoplasmantibod ANAC Section4Examplesofautoimmunediseases Examplesofautoimmunediseases 1 rheumatoidarthritis 2 systemlupuserythematosus 3 myastheniagravis 4 Grave sdisease 5 multiplesclerosis Rheumatoidarthritisnon suppurativeproliferativesynovitiswhichleadstodescructionofarticularcartilageandprogressivedisablingarthritisextra articularmanifestationsmaystronglyresembleSLEorsclerodermaoccursin1 ofpopulationusualonsetindecades4and53 5Xmorecommoninwomenthaninmen RheumatoidarthritisEtiologyandPathogenesisinitiatedbyactivationofT helpercellswhichproducecytokinesandactivateBcellstoproduceantibodiesHLA DR4 DR1associatedwithincreasedincidence80 ofpatientswithrhematoidfactors antibodiesagainstFcportionofIgG precisetriggerwhichinitatesdestructiveimmuneresponseisnotknown RhematoidarthritisClinicalcoursesymmetrical polyarticulararthritisweakness fever malaisemayaccompanyjointsymptomsstiffnessofjointsinAMearly thenprogressestoclaw likedeformitiesanemiaofchronicdiseasepresentinlatecasesseverelycripplingin15 20years lifeexpectancyreduced4 10yearsamyloidosisdevelopsin5 10 ofpatients RheumatoidarthritisPathologysymmetricarthritisaffectingprimarilysmalljoints proximalinterphalangealandmetacarpophalangealjoints chronicsynovitis proliferationofsynovialliningcells villousprojections subsynoviumfilledwithinflammatorycells lymphoidnodulespannus highlyvascularized inflamed reduplicatedsynoviumfibrosisandcalcificationfollowleadingtoankylosissynovialfluidcontainsneutrophils RheumatoidarthritisPathology continued rheumatoidnodules 25 ofpatients subcutaneousnodulesalongextensorsurfacesofforearmsorothersitesoftraumafirm non tender upto2cm diameterdermalnodulesoffibrinoidnecrosissurroundedbymacrophagesandgranulationtissueacutenecrotizingvasculitisofarteriesinfloridcasesprogressiveinterstitialfibrosisoflungsinsomecases Juvenilerheumatoidarthritischronicidiopathicarthritisinchildrensomevariantsinvolvefewlargejoints pauciarticular donothaverheum factorothersassoc withHLA B27uveitismaybepresentStill sdisease acutefebrileonset leukocytosis hepatosplenomegalyandlymphoadenopathyandskinrash ClassificationCriteriaforRheumatoidArthritis ARA 1987 Morningstiffness 1hourThreeormorejointareaarthritisHandarthritisSymmetricalinvolvementNodulesSerumrheumatoidfactorX raychanges 4ormorecriteriafor 6weeks rheumatoidarthritiswithsensitivity 77 95 specificity 85 98 MoensHJB etal JRheumatol1992 19 198 203 DoI DoesMyPatient HaveRheumatoidArthritis Unlikelyif NojointinflammationNosystemicsigns ExcesssystemicsignsNotsymmetricalAtypicaljointsinvolved 1 ofthepopulationhasrheumatoidarthritis Itisthemostcommonautoimmunearthritis butitisfarlesscommonthanosteoarthritisandothercausesofjointpain RheumatoidFactor IgM IgG FcReceptorofIgG TheRoleofRFTesting RFisthebest generallyavailable singletesttoassessprognosisinRARFhaslimitedutilityasadiagnostictestRFcorrelateswithdiseaseactivity butnotstrongly SystemicLupusErythematosus SLE multisystemautoimmunediseaseaffectsskin kidneys serosalsurfaces joints CNSandheartmanyautoantibodiesTable5 5 Kumar demonstratesdiagnosticcriteriaincidenceofupto1 2500people 10Xmorecommoninwomenusuallyarisesinsecond thirddecades morecommoninblackAmericans SLEEtiologyandPathogenesis failuretomaintainself tolerance SLEAntinuclearantibodiesantibodiestoDNAantibodiestohistonesantibodiestonon histoneproteinsboundtoRNAantibodiestonucleolarantigensANAtestissensitive butnotspecific SLEGeneticfactors30 concordanceinmonozygotictwinsassociationbetweenSLEandHLA DQloci SLENon geneticfactorsdrugssuchasprocainamideandhydralazinemaycauseLElikesignsandsymptomsandrogensprotect estrogensenhancelikelihoodofdevelopingLEUVlightmaytriggerdevelopmentofLE SLEImmunologicfactorsB cellhyperreactivityisafeatureofLE causedbyexcessT helperactivityhowself toleranceislostisnotknown SLEMechanismsoftissueinjurytypeIIIhypersensitivityreactionswithDNA anti DNAcomplexesdepositinginvesselsLEcell anyphagocyticleukocyte neutrophilormacrophage thatengulfsdenaturednucleiofinjuredcells evidenceofcellinjuryandexposednuclei SLEClinicalmanifestationsyoungwomen classicbutterflyrashonfacefever jointpain pleuriticchestpain photosensitivityrenalfailurehematologicanomaliesANAspresentin100 ofpatients anti double strandedDNAmuchmorespecificforLEsomewithrapiddownhillprogression10yearsurvivalis70 deathfromCNSandrenalinvolvement SLEVasculitis acutenecrotizingvasculitisofsmallarteriesorarteriolesinanyorgansSkinlesions erythematousmaculopapulareruptionovermalarregionswhichisexacerbatedbysun exposure liquefactivedegenerationofbasallayer interfacedermatitisandsuperficialanddeepperivascularlymphocyticinfiltratedepositsofimmunoglobulinsalongDEJsomepatientshavediscoidLEwithnosystemicinvolvement SLESerosalinvolvement pericardiumandpleuradevelopserosanguinousexudateNonbacterialverrucousendocarditis Libman Sacksendocarditis multiplewartydepositsonanyvalveandeithersurfaceoftheleafletsJointinvolvement nostrikinganatomicchangesnordeformities non specificlymphocyticinfiltratesCNSinvolvement multifocalcerebralinfarctsfrommicrovascularinjury SLERenalinvolvementmesangiallupusnephritis 20 ofcases mildsymptomsfocalproliferativeglomerulonephritis 25 ofcases mildclinicalsymptomsdiffuseproliferativeglomerulonephritis 45 50 ofcases verysymptomaticwithhematuria proteinuriaandhypertension renalfailuremembranousglomerulonephritis 15 ofcases severeproteinuriaandnephroticsyndrome Mechanismofmyastheniagravis Mech