An Eight-Gene Blood Expression Profile Predicts the Response to Infliximab in Rheumatoid Arthritis 英文参考文献.docVIP

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An Eight-Gene Blood Expression Profile Predicts the Response to Infliximab in Rheumatoid Arthritis 英文参考文献.doc

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An Eight-Gene Blood Expression Profile Predicts the Response to Infliximab in Rheumatoid Arthritis 英文参考文献

AnEight-GeneBloodExpressionProfilePredictsthe ResponsetoInfliximabinRheumatoidArthritis AntonioJulia`1,AlbaErra1,CarlesPalacio2,CarlosTomas2,XavierSans2,PereBarcelo′2,SaraMarsal1* 1GrupdeRecercadeReumatologia,InstitutdeRecercaHospitalUniversitariValld’Hebron,Barcelona,Spain,2Unitatd’Hematologia,HospitalUniversitariValld’Hebron, Barcelona,Spain Abstract Background:TNFalphablockadeagentslikeinfliximabareactuallythetreatmentofchoiceforthoserheumatoidarthritis (RA)patientswhofailstandardtherapy.However,aconsiderablepercentageofanti-TNFalphatreatedpatientsdonotshow asignificantclinicalresponse.GiventhatnewtherapiesfortreatmentofRAhavebeenrecentlyapproved,thereisapressing needtofindasystemthatreliablypredictstreatmentresponse.Wehypothesizedthattheanalysisofwholebloodgene expressionprofilesofRApatientscouldbeusedtobuildarobustpredictortoinfliximabtherapy. MethodsandFindings:WeperformedmicroarraygeneexpressionanalysisonwholebloodRNAsamplesfromRApatients startinginfliximabtherapy(n=44).Theclinicalresponsetoinfliximabwasdeterminedatweek14usingtheEULARcriteria. Blood cell populations were determined using flow cytometry at baseline, week 2 and week 14 of treatment. Using completecross-validationandrepeatedrandomsamplingweidentifiedarobust8-genepredictormodel(96.6%LeaveOne Outpredictionaccuracy,P=0.0001).ApplyingthismodeltoanindependentvalidationsetofRApatients,weestimatedan 85.7%predictionaccuracy(75–100%,95%CI).Inparallel,wealsoobservedasignificantlyhighernumberofCD4+CD25+ cells(i.e.regulatoryTcells)intherespondergroupcomparedtothenonrespondergroupatbaseline(P =0.0009). Conclusions:Thepresent8-genemodelobtainedfromwholebloodexpressionefficientlypredictsresponsetoinfliximabin RApatients.Theapplicationofthepresentsystemintheclinicalsettingcouldassisttheclinicianintheselectionofthe optimaltreatmentstrategyinRA. Citation: Julia` A, Erra A, Palacio C, Tomas C,Sans X, et al.(2009) An Eight-Gene BloodExpressionProfile Predicts the Response to Infliximab in Rheumatoid Arthritis.PLo