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

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.

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Fig. 1: Myeloid dendritic cells and FcɣRII expressing myeloid dendritic cells in PBMCs of HIV controller patients with various rs10800309 genotypes.

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Acknowledgements

This work was supported by the ANRS (Agence nationale de recherche sur le SIDA et les hépatites virales), the Investissements d’Avenir program managed by the Agence Nationale de la Recherche (ANR) under reference ANR-10-LABX-77 and EHVA (No. 681032, Horizon 2020). This work was further supported by grants from the ANR (ANR-11-LABX-0070_TRANSPLANTEX), INSERM UMR_S1109; the Institut Universitaire de France (IUF); and MSD Avenir grant (all to SB); the University of Strasbourg (IDEX UNISTRA, to RC and SB); and the INTERREG V European regional development fund (European Union) program project PERSONALIS (to RC and SB).

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Correspondence to Raphael Carapito or Christiane Moog.

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Carapito, R., Mayr, L., Molitor, A. et al. A FcɣRIIa polymorphism has a HLA-B57 and HLA-B27 independent effect on HIV disease outcome. Genes Immun 21, 263–268 (2020). https://doi.org/10.1038/s41435-020-0106-8

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