Measurement of soluble Fcγ receptor type IIIa derived from macrophages in plasma: increase in patients with rheumatoid arthritis

FcγRIII (CD16) is found in two alternative forms, a transmembrane FcγRIIIa expressed on NK cells and macrophages, and a glycosylphosphatidylinositol-linked FcγRIIIb present on neutrophils. Previously, we measured soluble FcγRIIIa (sFcγRIIIa) in plasma of NA(1 +, 2-) phenotyped donors with the anti-FcγRIII monoclonal antibody (MoAb) GRM1, which recognizes NA2-FcγRIIIb and FcγRIIIa. The level of sFcγRIIIa, as well as the total sFcγRIII (sFcγRIIIa plus sFcγRIIIb) in patients with rheumatoid arthritis (RA) was significantly higher than that in healthy controls. In this study, we measured sFcγRIIIa(Mφ) in plasma with a newly developed anti-FcγRIII MoAb, MKGR14 (mIgM), which recognizes FcγRIIIa(Mφ) specifically. From the recovery of purified sFcγRIIIa(Mφ), the amount of sFcγRIIIa(Mφ) present was about half that of sFcγRIIIa(NK), and that of sFcγRIIIa was about 50 times lower than that of sFcγRIIIb in pooled plasma from healthy NA(1 +, 2-) phenotyped donors. The level of sFcγRIIIa(Mφ) in RA patients was about four times higher than that in healthy controls. In RA patients, both the sFcγRIIIa(Mφ) and sFcγRIIIa levels were increased as proportionally as the Lansbury Index. The sFcγRIIIa, but not sFcγRIIIa(Mφ) levels, were increased directly proportional to C-reactive protein. sFcγRIIIa(Mφ) may be a novel marker of disease activity in RA

Soluble FcγRIIIaMφ Levels in Plasma Correlate with Carotid Maximum Intima-Media Thickness (IMT) in Subjects Undergoing an Annual Medical Checkup

Macrophages play a major role in the development of vascular lesions in atherogenesis. The cells express FcγRIIIa (CD16) identical to that in NK cells, but with a cell type-specific glycosylation, and these soluble forms (sFcγRIIIa) are present in plasma. We measured sFcγRIIIaMφ derived from macrophages in plasma from subjects undergoing an annual medical checkup. The levels of sFcγRIIIaMφ increased with age, and correlated positively with body mass index, blood pressure, LDL cholesterol to HDL cholesterol ratio, triglycerides, hemoglobin A1c, and creatinine, but negatively with HDL-cholesterol levels. The sFcγRIIIaMφ levels were related to the number of risk factors for atherosclerosis: such as aging, current smoking, diabetes, hypertension, hyper-LDL-cholesterolemia, hypo-HDL-cholesterolemia, and family history of atherosclerotic diseases. In addition, the sFcγRIIIaMφ levels were correlated with carotid maximum intima-media thickness (IMT). These findings indicate the macrophages are activated during the incipient stage of atherosclerosis, and suggest sFcγRIIIaMφ may be used as a predictive marker for atherosclerosis