Plasma levels of the soluble form of the FcγRIIa receptor vary with receptor polymorphisms and are elevated in rheumatoid arthritis.

Soluble forms of the low-affinity immunoglobulin receptor Fc gamma RIIa (sFc gamma RIIa) lacking the cytoplasmic tail have been reported in plasma however the mechanism and functional consequences are unknown. This study aimed to evaluate mechanisms of Fc gamma RIIa release compared to GPVI release from platelets, and examine whether genetic polymorphisms at positions 27 and 131 within Fc gamma RIIa correlate with platelet Fc gamma RIIa stability and function. Enzyme-linked immunosorbent assays (ELISAs) were used to measure plasma sFc gamma RIIa and sGPVI levels. Fc gamma RIIa genotype at positions 27 and 131 was evaluated. sFc gamma RIIa levels were not significantly different between non-131HH and 131HH but were significantly lower in 27W than non-27W. Treatment of platelets with aggregated immunoglobulin (Ig) G induced release of Fc gamma RIIa and GPVI, but only sGPVI release was statistically significant, required functional Fc gamma RIIa, and was blocked by inhibitors of signaling pathways and metalloproteinases. This indicated that sFc gamma RIIa was not released from platelets by metalloproteolysis. sFc gamma RIIa levels were not correlated with sGPVI levels in healthy individuals however levels of sFc gamma RIIa and sGPVI in plasma from patients with rheumatoid arthritis (RA) were significantly elevated above levels found in healthy individuals. Elevated level of sFc gamma RIIa in RA patients may reflect active immune-based arthritis and be predictive of active inflammation.