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

AIDS. 1995 Mar;9(3):229-34.

Abstract

Objectives: Expression of immunoglobulin (Ig) A Fc receptors (Fc alpha R) and their saturation by endogenous IgA were studied on blood monocytes and neutrophils to evaluate the role of Fc alpha R in the formation 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 quantitative flow cytometry method in which blood cells were stained with anti-Fc alpha R monoclonal antibodies (MAb) recognizing epitopes outside the IgA-binding site and with F(ab')2 fragments of anti-IgA antibodies. Immunoprecipitations of radiolabelled surface Fc alpha R molecules were analysed by sodium dodecylsulphate-polyacrylamide gel electrophoresis under glycosylated and deglycosylated conditions.

Results: This study reveals a diminished surface expression of Fc alpha R on blood monocytes of HIV-1-infected patients, which follows disease progression. Fc alpha R molecules on patients' neutrophils have a higher apparent molecular mass (60-90 kD) with normal protein core, suggesting expression of receptors with altered carbohydrate moieties. Increased levels of serum IgA significantly correlate with decreased levels of Fc alpha R in HIV-1-infected patients. Surface Fc alpha R molecules are saturated by endogenous IgA1 in both cell types.

Conclusion: These findings suggest that defective expression and/or altered glycosylation of Fc alpha R may result in receptor saturation, impairment of IgA catabolism and diminished clearance of IgA-IC in HIV-1-infected patients. Fc alpha R expression represents a new marker for disease progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Antibody Complex / blood
  • Biomarkers
  • Disease Progression
  • Female
  • Glycosylation
  • HIV Infections / immunology*
  • HIV Infections / physiopathology
  • HIV-1 / immunology*
  • Humans
  • Immunoglobulin A / blood*
  • Immunoglobulin A / immunology
  • Immunoglobulin A / metabolism
  • Immunoglobulin Fab Fragments
  • Male
  • Molecular Weight
  • Monocytes / immunology
  • Neutrophils / immunology
  • Receptors, Fc / analysis*
  • Receptors, Fc / metabolism

Substances

  • Antigen-Antibody Complex
  • Biomarkers
  • Immunoglobulin A
  • Immunoglobulin Fab Fragments
  • Receptors, Fc