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Increase of Soluble FcgRIIIa Derived from Natural Killer Cells and Macrophages in Plasma from Patients with Rheumatoid Arthritis
MIDORI MASUDA, TADANOBU MORIMOTO, MASJA DE HAAS, NORIKO NISHIMURA, KYOKO NAKAMOTO, KAZUYUKI OKUDA, YUTAKA KOMIYAMA, RYOKEI OGAWA, and HAKUO TAKAHASHI
ABSTRACT.
Objective. FcgRIII (CD16), one of the low affinity IgG Fc receptors, is found in 2 alternative forms, a transmembrane FcgRIIIa expressed on natural killer (NK) cells and macrophages, and a glycosylphosphatidylinositol-linked FcgRIIIb present on neutrophils. Both FcgRIII are released from the cell surface by proteolytic cleavage and these soluble forms (sFcgRIII) are present in plasma. Since NK cells and macrophages will be activated locally, leading to shedding of FcgRIIIa and its subsequent release into blood, we investigated whether sFcgRIIIa plasma concentrations would be a good marker for disease activity in patients with rheumatoid arthritis (RA). Methods. We measured sFcgRIIIa with an immuno-PCR in plasma of NA(1+,2–) phenotyped donors. In this assay, we used CD16 GRM1, which recognizes NA2-FcgRIIIb and FcgRIIIa. We also analyzed precipitated sFcgRIIIa derived from plasma with immunoblotting with CD16 CLB-LM6.30. Results. The concentration of sFcgRIIIa in patients with RA was about 3 times higher than in healthy controls. In controls, the sFcgRIIIa levels in plasma correlated with the number of NK cells in peripheral blood. In RA patients, sFcgRIIIa levels were increased directly proportionally to the concentrations of IgG, IgA, or IgM and to erythrocyte sedimentation rate or Lansbury Index. The electrophoretic mobility of plasma sFcgRIIIa corresponded with sFcgRIIIa derived from NK cells and/or macrophages. In general, plasma sFcgRIIIa originated from both cell types; however, the ratio of sFcgRIIIaNK to sFcgRIIIaMf varied in the RA patients. Conclusion. Increased sFcgRIIIa levels in RA patients were found to be caused by NK cell and/or macrophage activation. Plasma sFcgRIIIa levels may serve as a marker for disease activity in RA. (J Rheumatol 2003;30:1911-7) Key Indexing Terms:
MACROPHAGES
From the Departments of Clinical Sciences and Laboratory Medicine and Orthopaedic Surgery, Kansai Medical University, Osaka, Japan; and Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Sanquin Blood Supply Foundation, and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Amsterdam, The Netherlands. Supported in part by grants from the Ministry of Education, Grant-in-Aid for Scientific Research (C) (No. 07672505, 10672192 and 14572192), from the Charitable Trust Clinical Pathology Research Foundation of Japan, and from TERUMO Life Science Foundation (No. 99-319). M. Masuda, PhD, Associate Professor; N. Nishimura, BSc; K. Nakamoto, BSc; K. Okuda, BSc; Y. Komiyama, PhD, Associate Professor; H. Takahashi, MD, PhD, Professor, Department of Clinical Sciences and Laboratory Medicine, Kansai Medical University; T. Morimoto, MD, PhD, Associate Professor; R. Ogawa, MD, PhD, Professor, Department of Orthopaedic Surgery, Kansai Medical University; M. de Haas, MD, PhD, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service. Address reprint requests to Dr. M. Masuda, Departments of Clinical Sciences and Laboratory Medicine, Kansai Medical University, 10-15 Fumizonocho, Moriguchi, Osaka 570-8506, Japan. E-mail: masuda@takii.kmu.ac.jp Submitted June 24, 2002; revision accepted February 21, 2003. |