Rheumatoid peripheral blood phagocytes are primed for activation but have impaired Fc-mediated generation of reactive...

Significant levels of circulating immune complexes (ICs) containing rheumatoid factors and immunoglobulin G in peripheral blood are a characteristic feature of rheumatoid arthritis (RA). ICs interact through Fc gamma receptors (Fc gammaR) to activate phagocytes in numerous inflammatory processes. The high concentration of neutrophils in synovial fluid during active phases of the disease, together with their destructive capacity, pose important questions as to their role in the pathogenesis of RA. Functional defects in RA or control peripheral blood neutrophil Fc gammaRs were examined with a specific Fc gammaR-mediated reactive oxygen species (ROS) assay. Heterologous cross-linking of Fc gammaRIIa and Fc gammaRIIIb on neutrophils resulted in a significantly decreased production of ROS by RA cells compared with controls matched for age and sex. However, expression and homologous ligation of receptors did not differ between these groups. These data suggest that neutrophil priming does occur before emigration into the joint and that blood neutrophils from patients with RA have a functional impairment in cooperative Fc gammaR-mediated ROS generation. This may account for the increased susceptibility to bacterial infection that arises in patients with severe disease.