Introduction: FcgRIIa is a unique and the most widely expressed activating FcR in humans that avidly binds immune complexes and triggers inflammation. Polymorphisms of FcgRIIa (RR131 high responder; HH131 low responder) influence receptor function and are linked to susceptibility to infections or autoimmune diseases. On platelets, binding of ligands to either FcgRIIa or the structurally-related platelet-specific collagen receptor, GPVI, triggers platelet activation, aggregation and metalloproteinase-mediated ectodomain shedding of GPVI, generating soluble GPVI (sGPVI) in plasma. Soluble forms of FcgRIIa (sFcgRIIa) lacking the cytoplasmic tail have been reported in plasma however the mechanism of release and the functional consequences are unknown.

Aim: To evaluate plasma levels of sFcgRIIa and sGPVI and proteolytic mechanisms of release of FcgRIIa, as well as examine whether genetic polymorphisms at positions 27 and 131 within FcgRIIa correlate with platelet FcgRIIa and GPVI receptor stability and function, and compare levels of sFcgRIIa and sGPVI in plasma from patients with circulating levels of immune complexes.

Methods: ELISA was used to measure sFcgRIIa and sGPVI level and DNA sequencing was used to determine FcgRIIa genotype.

Results and conclusion: Genotype at position 131 and 27 influences platelet function and receptor stability of FcgRIIa in healthy individuals.However, release of FcgRIIa or GPVI from washed platelets after treatment for 3 h with aggregated IgG showed that release of GPVI but not FcgRIIa was blocked by metalloproteinase inhibitors (GM6001, GI254023, EDTA) or the Syk inhibitor, BAY61. Preliminary analysis reveals that elevated levels of sFcgRIIa and sGPVI in plasma from arthritis patients may reflect active immune-based arthritis and may be predictive of active inflammation.