EXTENDED REPORT

Differential effect of methotrexate on the increased CCR2 density on circulating CD4 T lymphocytes and monocytes in active chronic rheumatoid arthritis, with a down regulation only on monocytes in responders

T Ellingsen¹, N Hornung², B K Møller³, J H Poulsen⁴, K Stengaard-Pedersen¹

¹ Department of Rheumatology, Århus University Hospital, Århus C, Denmark
² Department of Clinical Biochemistry, Randers County Hospital, Randers, Denmark
³ Department of Clinical Immunology, Århus University Hospital, Århus C, Denmark
⁴ Department of Clinical Biochemistry, Hvidovre Hospital, Hvidovre, Denmark

Correspondence to:
Dr T Ellingsen
Department of Rheumatology, Århus University Hospital, Building 3 Nørrebrogade 44, DK-8000 Århus C, Denmark; torkell{at}dadlnet.dk

Objectives: To evaluate the effect of orally administered methotrexate (MTX) on the density of CC chemokine receptor 2 (CCR2) and CXC chemokine receptor 3 (CXCR3) on circulating monocytes, and the coexpression of CXCR3 and CCR2 on CD4 T lymphocytes in patients with active chronic rheumatoid arthritis.

Methods: All 34 patients with rheumatoid arthritis fulfilled the 1987 American Rheumatism Association criteria and were followed for 16 weeks after starting MTX. Peripheral blood mononuclear cells were analysed for CCR2 and CXCR3 density by three-colour flow cytometry before initiation of MTX and at week 12.

Results: 22 (65%) patients were non-responders, 12 (35%) patients responded to MTX by American College of Rheumatology (ACR)20% criteria, and 8 (24%) of these patients responded by ACR50%. In patients with active rheumatoid arthritis before starting MTX, CCR2 density on circulating monocytes, CD4+ CXCR3+ and CD4+ CXCR3– T lymphocytes was increased compared with controls. During 12 weeks of MTX treatment, the CCR2 density on monocytes decreased significantly in the ACR50% group but not in the ACR20% and non-responder groups. The increased CCR2 density on CD4+ CXCR3+ and CD4+ CXCR3– T lymphocytes was unaffected by the reduction in disease activity measured in relation to MTX treatment. The percentage of both monocytes and CD4+ CXCR3+ and CD4+ CXCR3– T lymphocytes among the peripheral circulating mononuclear cells did not change during MTX treatment.

Conclusions: Active chronic rheumatoid arthritis is characterised by enhanced CCR2 density on circulating monocytes and CD4+ CXCR3+ and CD4+ CXCR3– T lymphocytes. During MTX treatment, a decrease in CCR2 density on monocytes in the ACR50% responder group was associated with decreased disease activity. The increased CCR2 density on CD4+ CXCR3+ and CD4+ CXCR3– T lymphocytes was uninfluenced by MTX and disease activity.

Abbreviations: ACR, American College of Rheumatology; CCR2, CC chemokine receptor 2; CXCR3, CXC chemokine receptor 3; DMARD, disease-modifying anti-rheumatic drug; IgM-RF, rheumatoid factor; MCP1, monocyte chemoattractant protein 1; MTX, methotrexate; MWR, Mann–Whitney rank sum test; WSR, Wilcoxon’s signed rank test

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