Abstract

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

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