PAD4 is not essential for disease in the KBxN murine autoantibody-mediated model of arthritis 英文参考文献.docVIP

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PAD4 is not essential for disease in the KBxN murine autoantibody-mediated model of arthritis 英文参考文献.doc

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PAD4 is not essential for disease in the KBxN murine autoantibody-mediated model of arthritis 英文参考文献

Rohrbachetal.ArthritisResearchTherapy2012,14:R104 /content/14/3/R104 RESEARCH ARTICLE OpenAccess PAD4isnotessentialfordiseaseintheK/BxN murineautoantibody-mediatedmodelofarthritis AmandaSRohrbach1,SaskiaHemmers1,SanjaArandjelovic1,MaripatCorr2andKerriAMowen1* Abstract Introduction:Bothmurineandhumangenome-wideassociationstudieshaveimplicatedpeptidylarginine deiminase(PAD4)asasusceptibilitygeneinrheumatoidarthritis(RA).Inaddition,patientswithRAcommonlyhave autoantibodieswhichrecognizePAD4orand/orcitrullinatedpeptides.Thisstudyaimstoevaluatetheroleof PAD4intheeffectorphaseofarthritis. Methods:PAD4knockout(KO)andwildtype(WT)C57BL/6JmicewereinjectedwithK/BxNseratoinduce disease.Progressionofdiseasewasmonitoredbymeasuringpawandankleswellingandclinicalindexesof disease,andpathogenesiswasassessedbyindexingofclinicalprogressiononpawscollectedfromWTandPAD4 KOmiceinjectedwithK/BxNserum.PAD4activitywasdeterminedbyvisualizationofneutrophilextracellulartraps (NETs)andimmunohistologicalanalysisofhistonecitrullination. Results:PAD4activityisreadilydetectableintheinflamedsynoviumofWTbutnotPAD4deficientanimals,as demonstratedbyhistonecitrullinationandNETformation.However,PAD4WTandKOanimalsdevelopK/BxN serumtransferdiseasewithcomparableseverityandkinetics,withnostatisticallysignificantdifferencesnotedin clinicalscores,swelling,jointerosionorjointinvasion. Conclusions:PAD4WTandKOmicedevelopdiseaseintheK/BxNserumtransfermodelofarthritiswithsimilar severityandkinetics,indicatingthatPAD4isdispensableinthiseffectorphasemodelofdisease. Introduction anti-citrullinated peptide antibodies (ACPAs) exhibit Citrulline-containing proteins are generated through highspecificity and sensitivity as diagnostic markers of posttranslational modification of arginine residues in a the disease [7]. Anti-citrulline peptide antibodies can reactioncatalyzedbytheCa2+-dependentpeptidylargi- appearbeforediseaseonsetandcorrelatewiththemost nine deiminases (PADs). There are five PAD family erosiveformo