Novel Biomarkers Distinguishing Active Tuberculosis from Latent Infection Identified by Gene Expression Profile of Peripheral Blood Mononuclear Cells 英文参考文献.docVIP

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Novel Biomarkers Distinguishing Active Tuberculosis from Latent Infection Identified by Gene Expression Profile of Peripheral Blood Mononuclear Cells 英文参考文献.doc

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Novel Biomarkers Distinguishing Active Tuberculosis from Latent Infection Identified by Gene Expression Profile of Peripheral Blood Mononuclear Cells 英文参考文献

NovelBiomarkersDistinguishingActiveTuberculosis fromLatentInfectionIdentifiedbyGeneExpression ProfileofPeripheralBloodMononuclearCells ChanyiLu1,2,JingWu1,2,HonghaiWang2,SenWang1,NiDiao1,FeifeiWang1,YanGao1,JiazhenChen1, LingyunShao1,XinhuaWeng1,YingZhang1,3*,WenhongZhang1,4 * 1DepartmentofInfectiousDiseases,HuashanHospital,FudanUniversity,Shanghai,China,2StateKeyLaboratoryofGeneticEngineering(SKLGE),InstituteofGenetics, SchoolofLifeSciences,FudanUniversity,Shanghai,China,3DepartmentofMolecularMicrobiologyandImmunology,BloombergSchoolofPublicHealth,JohnsHopkins University,Baltimore,Maryland,UnitedStatesofAmerica,4InstitutesofBiomedicalSciences,FudanUniversity,Shanghai,China Abstract Background:HumansinfectedwithMycobacteriumtuberculosis(MTB)candeletethepathogenorotherwisebecomelatent infectionoractivedisease.However,thefactorsinfluencingthepathogenclearanceanddiseaseprogressionfromlatent infectionarepoorlyunderstood.Thisstudyattemptedtouseagenome-widetranscriptomeapproachtoidentifyimmune factorsassociatedwithMTBinfectionandnovelbiomarkersthatcandistinguishactivediseasefromlatentinfection. Methodology/PrincipalFindings:Usingmicroarrayanalysis,wecomprehensivelydeterminedthetranscriptionaldifference inpurifiedproteinderivative(PPD)stimulatedperipheralbloodmononuclearcells(PBMCs)in12individualsdividedinto three groups: TB patients (TB), latent TB infection individuals (LTBI) and healthy controls (HC) (n=4 per group). A transcriptional profiling of 506 differentially expressed genes could correctly group study individuals into three clusters. Moreover, 55- and 229-transcript signatures for tuberculosis infection (TBLTBI) and active disease (TB) were identified, respectively. The validation study by quantitative real-time PCR (qPCR) performed in 83 individuals confirmed the expressionpatternsof81%ofthemicroarrayidentifiedgenes.DecisiontreeanalysisindicatedthatthreegenesofCXCL10, ATP10AandTLR6coulddifferentiateTBfromLTBIsubjects.Additionalvalidationwasperformedtoassessth