title: Impaired Fc alpha receptor expression is linked to increased immunoglobulin A levels and disease progression in HIV-1-infected patients.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: INSERM Unit 25, Necker Hospital, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Grossetête
authors.forename: J P
authors.initials: JP
authors.lastname: Viard
authors.forename: A
authors.initials: A
authors.lastname: Lehuen
authors.forename: J F
authors.initials: JF
authors.lastname: Bach
authors.forename: R C
authors.initials: RC
authors.lastname: Monteiro
mesh_terms: D000936:Antigen-Antibody Complex / Q000097:blood; D015415:Biomarkers; D018450:Disease Progression; D005260:Female; D006031:Glycosylation; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D007140:Immunoglobulin Fab Fragments; D008297:Male; D008970:Molecular Weight; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D011961:Receptors, Fc / Q000032:analysis* / Q000378:metabolism
chemical_list: D000936:Antigen-Antibody Complex; D015415:Biomarkers; D007070:Immunoglobulin A; D007140:Immunoglobulin Fab Fragments; D011961:Receptors, Fc