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

Abstract

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

FcγR expression on NK cells influences disease severity in rheumatoid arthritis

“…The reduction in CD16 expression might be correlated with the recent description of significant levels of soluble CD16 in the serum of RA patients. 33 Abnormal distribution of FccRIIC alleles in RA patients We next carried out molecular analysis of the CD32 isoforms expressed by RA patients and normal donors. An allelic polymorphism in the FcgRIIC gene at amino acid 13 (FcgRIIC-13), which falls in the first extracellular domain, determines the presence or absence of CD32 on NK cells.…”

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

“…The total sFcγRIII concentrations were measured by enzyme-linked immunosorbent assay (ELISA) as described before (21). Briefly, an ELISA plate (Nunc Immunoplate Maxisorp, Roskilde, Denmark) was coated with an anti-FcγRIII mAb, CLBFcRgranI, which recognizes all types of FcγRIIIs and was used as a capture antibody (Figure 1).…”

“…A calibration curve was constructed with pooled plasma from healthy donors and the concentration of sFcγRIIIs in this pool was set at 100 arbitrary units (AU), as described before (15,16,21). So the sFcγRIIIa Mφ or total sFcγRIII concentrations are presented as the percentage of sFcγRIII compared with the amount of sFcγRIII in the pooled plasma.…”

“…Recently, we have succeeded in raising a new anti-FcγRIII monoclonal antibody (mAb), MKGR14, which specifically recognizes FcγRIIIa Mφ (15). …”

Site-Specific Classification of N -Linked Oligosaccharides of the Extracellular Regions of Fcγ Receptor IIIb Expressed in Baby Hamster Kidney Cells

“…For example, FcγRIII contains two isoforms that are encoded by two individual genes: transmembrane FcγRIIIa and glycosylphosphatidylinositol-linked FcγRIIIb. Both FcγRIII isoforms can exist as a soluble form (sFcγRIII) that consists of an extracellular region proteolytically cleaved from the transmembrane segment [5][6][7].…”