B. Grossetete et al., IMPAIRED FC-ALPHA RECEPTOR EXPRESSION IS LINKED TO INCREASED IMMUNOGLOBULIN-A LEVELS AND DISEASE PROGRESSION IN HIV-1-INFECTED PATIENTS, AIDS, 9(3), 1995, pp. 229-234
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.