A FcɣRIIa polymorphism has a HLA-B57 and HLA-B27 independent effect on HIV disease outcome

Genes Immun. 2020 Aug;21(4):263-268. doi: 10.1038/s41435-020-0106-8. Epub 2020 Aug 5.

Abstract

Fcɣ receptors (FcɣRs) are key immune regulatory receptors that connect antibody-mediated immune responses to cellular effector functions. They are involved in the control of various immune functions including responses to infections. Genetic polymorphisms of FcɣRs coding genes (FCGR) have been associated with the regulation of HIV infection and progression. In this study, we analyzed the potential impact of five candidate FcɣR SNPs on viral control by genotyping 251 HIV controllers and 250 progressors. The rs10800309 AA genotype of the FcɣRIIa coding gene FCGR2A was found to be significantly associated with HIV control and this association was independent of HLA-B57 and HLA-B27 (OR, 2.84; 95% CI, 1.20-6.89; Pcor = 0.033). We further confirmed the functional role of this polymorphism by showing an association of this same AA genotype with an increased in vitro FcɣRII expression on myeloid cells including dendritic cells (P = 0.0032). Together, these results suggest that the AA genotype of rs10800309 confers an improved immune response through FcɣRII upregulation and that this polymorphism may serve as an additional predictive marker of HIV control.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology
  • Cohort Studies
  • Disease Progression
  • Female
  • Genetic Association Studies
  • HIV Infections / genetics*
  • HIV Infections / immunology*
  • HIV-1 / immunology
  • HIV-1 / physiology
  • HLA-B Antigens / immunology*
  • HLA-B27 Antigen / immunology*
  • Host Microbial Interactions
  • Humans
  • Male
  • Middle Aged
  • Myeloid Cells
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide
  • Receptors, IgG / genetics*
  • Receptors, IgG / metabolism*
  • Viral Load
  • Virus Replication

Substances

  • Fc gamma receptor IIA
  • HLA-B Antigens
  • HLA-B27 Antigen
  • HLA-B57 antigen
  • Receptors, IgG