Renal expression and serum levels of high mobility group box 1 protein in lupus nephritis 英文参考文献.docVIP

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Renal expression and serum levels of high mobility group box 1 protein in lupus nephritis 英文参考文献.doc

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Renal expression and serum levels of high mobility group box 1 protein in lupus nephritis 英文参考文献

Zickertetal.ArthritisResearchTherapy2012,14:R36 /content/14/1/R36 RESEARCH ARTICLE OpenAccess Renalexpressionandserumlevelsofhigh mobilitygroupbox1proteininlupusnephritis AgnetaZickert1*,KarinPalmblad2,BirgittaSundelin3,SangeetaChavan4,KevinJTracey4,AnnetteBruchfeld5and IvaGunnarsson1 Abstract Introduction:Highmobilitygroupbox1protein(HMGB1)isanuclearDNAbindingproteinactingasapro- inflammatorymediatorfollowingextracellularrelease.HMGB1hasbeenincreasinglyrecognizedasapathogenic mediatorinseveralinflammatorydiseases.ElevatedserumlevelsofHMGB1havebeendetectedinautoimmune diseasesincludingSystemiclupuserythematosus(SLE).However,thelocalexpressionofHMGB1inactivelupus nephritis(LN)isnotknown.HereweaimedtostudybothtissueexpressionandserumlevelsofHMGB1inLN patientswithactivediseaseandafterinductiontherapy. Methods:Thirty-fivepatientswithactiveLNwereincluded.Renalbiopsieswereperformedatbaselineandafter standardinductiontherapy;corticosteroidscombinedwithimmunosuppressivedrugs.Thebiopsieswereevaluated accordingtotheWorldHealthOrganization(WHO)classificationandrenaldiseaseactivitywasestimatedusingthe BritishIsleslupusassessmentgroup(BILAG)index.SerumlevelsofHMGB1wereanalysedbywesternblot.HMGB1 expressioninrenaltissuewasassessedbyimmunohistochemistryatbaselineandfollow-upbiopsiesin25patients. Results:BaselinebiopsiesshowedWHOclassIII,IVorVandallpatientshadhighrenaldiseaseactivity(BILAGA/B). Follow-upbiopsiesshowedWHOItoII(n=14),III(n=6),IV(n=3)orV(n=12),and15/35patientswere regardedasrenalresponders(BILAGC/D). AtbaselineHMGB1wassignificantlyelevatedinserumcomparedtohealthycontrols(P0.0001).Inallpatients, serumlevelsdecreasedonlyslightly;however,inpatientswithbaselineWHOclassIVasignificantdecreasewas observed(P=0.03).ImmunostainingrevealedapronouncedextranuclearHMGB1expressionpredominantly outliningtheglomerularendotheliumandinthemesangium.TherewasnocleardifferenceinHMGB1expression comparingbaselineandfollow-upbiopsiesoranyapparentassociationtohistopathologicalclassificationo