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

OBJECTIVE

Expression of IgA Fc receptors (CD89, FcalphaR) and their occupancy by endogenous IgA were studied on blood monocytes and neutrophits to determine if FcalphaR defects could account for enhanced serum IgA and IgA-IC commonly found in patients with ankylosing spondylitis (AS).

METHODS

Peripheral blood samples were obtained from 34 patients with AS, 15 patients with rheumatoid arthritis, and 34 healthy individuals. Cell surface FcalphaR was analyzed using a quantitative flow cytometry method in which blood cells were stained with anti-FcalphaR monoclonal antibodies recognizing epitopes outside the IgA binding site and with F(ab')2 fragments of anti-IgA antibodies. Modulation of cell surface FcalphaR was evaluated after incubation of blood cells at 37 degrees C in absence of plasma. Biochemical characterization of iodinated FcalphaR molecules was determined by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).

RESULTS

FcaR expression was significantly decreased on monocytes and neutrophils in patients with AS compared to control groups. FcalphaR levels were inversely correlated with serum IgA, suggesting its negative regulatory role. Modulation experiments resulted in rapid and higher FcalphaR upregulation in AS than in controls, indicating that these molecules were downregulated only at the cell surface. Moreover, analysis of the surface iodinated FcalphaR molecules by SDS-PAGE revealed higher Mr (60-90 kDa) in AS than controls (55-75 kDa), also suggesting an altered glycosylation. Analysis of receptor occupancy revealed high levels of endogenous IgA bound to monocytes and neutrophils in patients with AS, pointing to a saturation of IgA Fc receptors.

CONCLUSION

We observed impaired expression of FcalphaR in patients with AS that is characterized by a downregulation process associated with post-translational alterations and enhanced binding of endogenous IgA. These alterations might lead to a defective blood clearance by FcalphaR resulting in the enhancement of IgA and IgA-IC in AS patients. Decreased FcalphaR expression represents a new marker for this disease.