Impaired expression of IgA Fc receptors (CD89) by blood phagocytic cells in ankylosing spondylitis

Objective. Expression of IgA Fc receptors (CD89, Fc alpha R) and their occu pancy by endogenous IgA were studied on blood monocytes and neutrophils to determine if Fc alpha R defects could account for enhanced serum IgA and Ig A-IC commonly found in patients with ankylosing spondylitis (AS). Methods. Peripheral blood samples were obtained from 34 patients with AS, 1 5 patients with rheumatoid arthritis, and 34 healthy individuals. Cell surf ace Fc alpha R was analyzed using a quantitative flow cytometry method in w hich blood cells were stained with anti-Fc alpha R monoclonal antibodies re cognizing epitopes outside the IgA binding site and with F(ab')(2) fragment s of anti-IgA antibodies. Modulation of cell surface Fc alpha R was evaluat ed after incubation of blood cells at 37 degrees C in absence of plasma. Bi ochemical characterization of iodinated Fc alpha R molecules was determined by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel elect rophoresis (SDS-PAGE). Results. Fc alpha R expression was significantly decreased on monocytes and neutrophils in patients with AS compared to control groups, Fc alpha R lev els were inversely correlated with serum IgA, suggesting its negative regul atory role. Modulation experiments resulted in rapid and higher Fc alpha R upregulation in AS than in controls, indicating that these molecules were d ownregulated only at the cell surface. Moreover, analysis of the surface io dinated Fc alpha R molecules by SDS-PAGE revealed higher M-r (60-90 kDa) in AS than controls (55-75 kDa), also suggesting an altered glycosylation. An alysis of receptor occupancy revealed high levels of endogenous IgA bound t o monocytes and neutrophils in patients with AS, pointing to a saturation o f IgA Fc receptors. Conclusion. We observed impaired expression of Fc alpha R inpatients with A S that is characterized by a downregulation process associated with post-tr anslational alterations and enhanced binding of endogenous IgA, These alter ations might lead to a defective blood clearance by Fc alpha R resulting in the enhancement of IgA and IgA-IC in AS patients. Decreased Fc alpha R exp ression represents a new marker for this disease.