IMPAIRED FC-ALPHA RECEPTOR EXPRESSION IS LINKED TO INCREASED IMMUNOGLOBULIN-A LEVELS AND DISEASE PROGRESSION IN HIV-1-INFECTED PATIENTS

Objectives: Expression of immunoglobulin (Ig) A Fc receptors (Fc alpha R) and their saturation by endogenous IgA were studied on blood monoc ytes and neutrophils to evaluate the role of Fc alpha R in the formati on of increased serum levels of IgA 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 quantitat ive flow cytometry method in which blood cells were stained with anti- Fc alpha R monoclonal antibodies (MAb) recognizing epitopes outside th e IgA-binding site and with F(ab')(2) fragments of anti-IgA antibodies . Immunoprecipitations of radiolabelled surface Fc alpha R molecules w ere analysed by sodium dodecylsulphate-polyacrylamide gel electrophore sis under glycosylated and deglycosylated conditions. Results: This st udy reveals a diminished surface expression of Fc alpha R on blood mon ocytes of HIV-1-infected patients, which follows disease progression. Fc alpha R molecules on patients' neutrophils have a higher apparent m olecular mass (60-90 kD) with normal protein core, suggesting expressi on of receptors with altered carbohydrate moieties. Increased levels o f serum IgA significantly correlate with decreased levels of Fc alpha R in HIV-1-infected patients. Surface Fc alpha R molecules are saturat ed by endogenous IgA1 in both cell types. Conclusion: These findings s uggest that defective expression and/or altered glycosylation of Fc al pha R may result in receptor saturation, impairment of IgA catabolism and diminished clearance of IgA-IC in HIV-1-infected patients. Fc alph a R expression represents a new marker for disease progression.