Impaired Fcα receptor expression is linked to increased immunoglobulin A levels and disease progression in HIV-1-infected patients

Abstract

Objectives: Expression of immunoglobulin (Ig) A Fc receptors (FcαR) and their saturation by endogenous lgA were studied on blood monocytes and neutrophils to evaluate the role of FcαR in the formation of increased serum levels of lgA and IgA-immune complexes (IgA-IC) observed during HIV-1 infection. Methods: Peripheral blood samples were obtained from 45 patients at different stages of HIV-1 infection and from 22 healthy volunteers. This study was performed using a quantitative flow cytometry method in which blood cells were stained with anti-FcαR monoclonal antibodies (MAb) recognizing epitopes outside the IgA-binding site and with F(ab')2 fragments of anti-IgA antibodies. Immunoprecipitations of radiolabelled surface FcαR molecules were analysed by sodium dodecylsulphate-polyacrylamide gel electrophoresis under glycosylated and deglycosylated conditions. Results: This study reveals a diminished surface expression of FcαR on blood monocytes of HIV-1-infected patients, which follows disease progression. FcαR molecules on patients' neutrophils have a higher apparent molecular mass (60-90kD) with normal protein core, suggesting expression of receptors with altered carbohydrate moieties. Increased levels of serum IgA significantly correlate with decreased levels of FcαR in HIV-1-infected patients. Surface FcαR molecules are saturated by endogenous IgA1 in both cell types. Conclusion: These findings suggest that defective expression and/or altered glycosylation of FcαR may result in receptor saturation, impairment of IgA catabolism and diminished clearance of IgA-IC in HIV-1-infected patients. FcαR expression represents a new marker for disease progression.