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Longitudinal study of chemokine receptor expression on peripheral lymphocytes in multiple sclerosis: CXCR3 upregulation is associated with relapse

Division of Biomedical Sciences, Sheffield Hallam University, Howard Street, Sheffield, S1 1WB, UK, Department of Neurology, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF, UK

J Lawry

Institute for Cancer Studies, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK

S JL Howell

Department of Neurology, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF, UK

M N Woodroofe

Division of Biomedical Sciences, Sheffield Hallam University, Howard Street, Sheffield, S1 1WB, UK, n.woodroofe{at}shu.ac.uk

The interaction between chemokines and their recepto rs leads to selective recruitment of cells to foci of inflammation. C ross-sectional studies have reported significantly different expression of chemokine recepto rs C XC R3, C C R5 and C C R2 on peripheral blood lymphocytes in multiple sclerosis (MS) compared with controls. C ells expressing these receptors are likely to play a pathogenic role as suggested by studies of experimental autoimmune encephalo myelitis. A lso, immunogenetic studies of nonfunctional C C R5 recepto rs in MS patients, due to 32d deletion, demonstrated a delay in time to next relapse. The aims of this study were to detect any changes in the serial expression of chemokine recepto rs C C R2, C C R3, C C R5 and C XCR3 on peripheral blood C D4 lymphocytes from patients with MS and to correlate the changes with relapses. Upregulation of C XCR3 expression on peripheral blood C D4 lymphocytes was associated with all relapses and C C R5 expression was significantly affected with all relapses. C linical recovery, with or without intravenous methylprednisolone treatment, coincided with the return of C XC R3 towards baseline in all but one case. Fluctuation in the expression of C XC R3 and C C R5 was also significantly greater in clinically stable patients with MS compared with controls, which may be due to subclinical disease activity. These findings provide further support for the view that C XC R3 and C C R5 antagonists could have a therapeutic value in MS.

Key Words: chemokine receptors • CCR5 • CXCR3 • longitudinal • multiple sclerosis

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