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Enhanced Fcg Receptor I, aMß2 Integrin Receptor Expression by Monocytes and Neutrophils in Rheumatoid Arthritis: Interaction with Platelets

ANDREIA BUNESCU, PETER SEIDEMAN, RODICA LENKEI, KLAS LEVIN, and NILS EGBERG

ABSTRACT.

Objective.
To investigate platelet and leukocyte activation and interaction in patients with rheumatoid arthritis (RA) and the effect of methotrexate (MTX) or anti-tumor necrosis factor-a (TNF-a) treatment on these variables.

Methods. Four-color flow cytometry analysis was performed for quantitative measurement of platelet (P-selectin, PAC-1) and leukocyte (CD11b, CD64) activation markers and estimation of percentage of leukocyte-platelet complexes in whole blood in 20 patients with RA before and after 6 weeks of therapy and in 20 controls. In addition, measures of soluble P-selectin (sP-selectin), ß-thromboglobulin, fibrinogen, prothrombin fragment 1+2, D-dimer, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), and TNF-a and tender and swollen joint counts were carried out.

Results. Before therapy, PAC-1 binding, expression of CD11b and CD64 on monocytes and neutrophils, circulating levels of monocyte (CD11b+ or CD64+)-platelet complexes, monocyte-PAC-1+ platelet complexes, CRP, ESR, IL-6, TNF-a, fibrinogen, D-dimer and sP-selectin were significantly higher in RA patients compared to controls. The anti-TNF-a therapy significantly reduced levels of monocyte-PAC-1+ platelet complexes, sP-selectin, CRP, ESR, IL-6, TNF-a, fibrinogen, and D-dimer and tender and swollen joint counts. CD64 expression on monocytes was significantly decreased by MTX therapy. PAC-1 binding was not inhibited by MTX or anti-TNF-a.

Conclusion. Increased platelet and leukocyte activation and increased formation of leukocyte-platelet complexes in patients with RA suggest a status of simultaneous activation of the immune and hemostatic systems. (J Rheumatol 2004;31:2347-55)

Key Indexing Terms:

RHEUMATOID ARTHRITIS
FLOW CYTOMETRY
PLATELET
LEUKOCYTE ACTIVATION


From the Department of Clinical Chemistry, Capio Diagnostik, St. Göran's Hospital; Reumacenter, Sabbatsberg Hospital; and the Departments of Medicine and Clinical Chemistry, Karolinska Institute, Stockholm, Sweden.

Supported by Capio Diagnostik, Stockholm, Sweden.

A. Bunescu, MD, Department of Clinical Chemistry, Capio Diagnostik, St. Göran's Hospital; P. Seideman, MD, PhD, Associate Professor, Reumacenter, Sabbatsberg Hospital, Department of Medicine, Karolinska Institute; R. Lenkei, MD, PhD, Flow Cytometry Laboratory, Capio Diagnostik, St. Göran's Hospital; K. Levin, MD, PhD, Department of Clinical Chemistry, Capio Diagnostik, St. Göran's Hospital; N. Egberg, MD, PhD, Associate Professor, Department of Clinical Chemistry, Karolinska Hospital.

Address reprint requests to Dr. A. Bunescu, Department of Clinical Chemistry, Capio Diagnostik, St. Göran's Hospital, 11281 Stockholm, Sweden. E-mail: Andreia.Bunescu@capio.se

Submitted July 10, 2003; revision accepted June 9, 2004.




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