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.
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