A Plasma Biomarker Signature of Immune Activation in HIV Patients on Antiretroviral Therapy 英文参考文献.docVIP

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A Plasma Biomarker Signature of Immune Activation in HIV Patients on Antiretroviral Therapy 英文参考文献.doc

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A Plasma Biomarker Signature of Immune Activation in HIV Patients on Antiretroviral Therapy 英文参考文献

APlasmaBiomarkerSignatureofImmuneActivationin HIVPatientsonAntiretroviralTherapy AnupaKamat1,2,VikasMisra1,EdanaCassol1,2,PetronelaAncuta3,ZhenyuYan4,ChengLi4 ,Susan Morgello5,DanaGabuzda1,2* 1Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts, United States of America, 2Harvard Medical School, Boston, Massachusetts,UnitedStatesofAmerica,3DepartmentofMicrobiologyandImmunology,FacultyofMedicine,CHUM-ResearchCenter,Universite′deMontre′al,Montreal, Canada,4DepartmentofBiostatistics,DanaFarberCancerInstitute,Boston,Massachusetts,UnitedStatesofAmerica,5MountSinaiMedicalCenter,NewYork,United StatesofAmerica Abstract Background: Immune activation is a strong predictor of disease progression in HIV infection. Combinatorial plasma biomarkersignaturesthatrepresentsurrogatemarkersofimmuneactivationinbothviremicandaviremicHIVpatientson combination antiretroviral therapy (cART) have not been defined. Here, we identify a plasma inflammatory biomarker signaturethatdistinguishesbetweenbothviremicandaviremicHIVpatientsoncARTandhealthycontrolsandexamine relationshipsofthissignaturetomarkersofdiseaseprogression. Methods:MultiplexprofilingandELISAwereusedtodetect15cytokines/chemokines,solubleIL-2R(sIL-2R),andsoluble CD14 (sCD14) in plasma from 57 HIV patients with CD4 nadir ,300 cells/ml and 29 healthy controls. Supervised and unsupervisedanalyseswereusedtoidentifybiomarkersexplainingvariancebetweengroupsdefinedbyHIVstatusordrug abuse.RelationshipsbetweenbiomarkersanddiseasemarkerswereexaminedbySpearmancorrelation. Results: The majority (91%) of HIV subjects were on cART, with 38% having undetectable viral loads (VL). Hierarchical clustering identified a biomarker cluster in plasma consisting of two interferon-stimulated gene products (CXCL9 and CXCL10), T cell activation marker (sIL-2R), and monocyte activation marker (sCD14) that distinguished both viremic and aviremicHIVpatientsoncARTfromcontrols(p,0.0001)andweretop-rankedinvariablesimpor