FcγRIIIa Expression on Monocytes in Rheumatoid Arthritis Role in Immune-Complex Stimulated TNF Production and Non-Response to Methotrexate Therapy 英文参考文献.docVIP

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FcγRIIIa Expression on Monocytes in Rheumatoid Arthritis Role in Immune-Complex Stimulated TNF Production and Non-Response to Methotrexate Therapy 英文参考文献.doc

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FcγRIIIa Expression on Monocytes in Rheumatoid Arthritis Role in Immune-Complex Stimulated TNF Production and Non-Response to Methotrexate Therapy 英文参考文献

FccRIIIaExpressiononMonocytesinRheumatoid Arthritis:RoleinImmune-ComplexStimulatedTNF ProductionandNon-ResponsetoMethotrexateTherapy DawnL.Cooper1,StephenG.Martin1,JamesI.Robinson1,SarahL.Mackie1,ChristopherJ.Charles1, JackieNam1,YEARConsortium2,JohnD.Isaacs3,PaulEmery1,AnnW.Morgan1* 1NIHR-Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Leeds, United Kingdom, 2YEAR Consortium, 3Institute of Cellular Medicine, Newcastle University,NewcastleuponTyne,UnitedKingdom Abstract Objective: The expression of FccRIIIa/CD16 may render monocytes targets for activation by IgG-containing immune complexes(IC).WeinvestigatedwhetherFccRIIIa/CD16wasupregulatedinrheumatoidarthritis(RA),associatedwithTNF productioninresponsetoIC-stimulation,andifthispredictedresponsetomethotrexatetherapy. Methods: FccRIIIa/CD16 expression on CD14low and CD14++ monocytes was measured by flow cytometry in healthy controlsandRApatients(earlyandlong-standingdisease).IntracellularTNF-stainingwascarriedoutafter invitroLPSor heat-aggregatedimmunoglobulin(HAG)activation.FccRIIIa/CD16expressionpre-andpost-steroid/methotrexatetreatment wasexamined. Results:IncreasedFccRIIIa/CD16expressiononCD14++monocytesinlong-standingRApatientscomparedtocontrolswas demonstrated (p=0.002) with intermediate levels in early-RA patients. HAG-induced TNF-production in RA patients was ++ ++ correlated with the percentage of CD14 monocytes expressing FccRIIIa/CD16 (p,0.001). The percentage of CD14 monocytesexpressingFccRIIIa/CD16atbaselineinearlyDMARD-na?¨veRApatientswasnegativelycorrelatedwithDAS28- ESRimprovement14-weekspost-methotrexatetherapy(p=0.003)andwassignificantlyincreasedinEULARnon-responders compared to moderate (p=0.01) or good responders (p=0.003). FccRIIIa/CD16 expression was not correlated with age, presenceofsystemicinflammationorautoantibodytiters. Conclusion: Increased FccRIIIa/CD16 expression on CD14++ monocytes in RA may result in a cell that has increased responsivenesstoIC-stimulati