Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

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

Genes & Immunity volume 21, pages 263–268 (2020)Cite this article

Subjects

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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

Similar content being viewed by others

References

  1. Su B, Dispinseri S, Iannone V, Zhang T, Wu H, Carapito R, et al. Update on Fc-mediated antibody functions against HIV-1 beyond neutralization. Front Immunol. 2019;10:2968.

    Article  CAS  Google Scholar 

  2. Moog C, Dereuddre-Bosquet N, Teillaud JL, Biedma ME, Holl V, Van Ham G, et al. Protective effect of vaginal application of neutralizing and nonneutralizing inhibitory antibodies against vaginal SHIV challenge in macaques. Mucosal Immunol. 2014;7:46–56.

    Article  CAS  Google Scholar 

  3. Burton DR, Hessell AJ, Keele BF, Klasse PJ, Ketas TA, Moldt B, et al. Limited or no protection by weakly or nonneutralizing antibodies against vaginal SHIV challenge of macaques compared with a strongly neutralizing antibody. Proc Natl Acad Sci USA. 2011;108:11181–6.

    Article  CAS  Google Scholar 

  4. Horwitz JA, Bar-On Y, Lu CL, Fera D, Lockhart AAK, Lorenzi JCC, et al. Non-neutralizing antibodies alter the course of HIV-1 infection in vivo. Cell. 2017;170:637–48. e10.

    Article  CAS  Google Scholar 

  5. Haynes BF, Gilbert PB, McElrath MJ, Zolla-Pazner S, Tomaras GD, Alam SM, et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med. 2012;366:1275–86.

    Article  CAS  Google Scholar 

  6. Mayr LM, Decoville T, Schmidt S, Laumond G, Klingler J, Ducloy C, et al. Non-neutralizing antibodies targeting the V1V2 domain of HIV exhibit strong antibody-dependent cell-mediated cytotoxic activity. Sci Rep. 2017;7:12655.

    Article  Google Scholar 

  7. Lambotte O, Pollara J, Boufassa F, Moog C, Venet A, Haynes BF, et al. High antibody-dependent cellular cytotoxicity responses are correlated with strong CD8 T cell viral suppressive activity but not with B57 status in HIV-1 elite controllers. PloS ONE. 2013;8:e74855.

    Article  CAS  Google Scholar 

  8. Ackerman ME, Mikhailova A, Brown EP, Dowell KG, Walker BD, Bailey-Kellogg C, et al. Polyfunctional HIV-specific antibody responses are associated with spontaneous HIV control. PLoS Pathog. 2016;12:e1005315.

    Article  Google Scholar 

  9. Bruhns P, Iannascoli B, England P, Mancardi DA, Fernandez N, Jorieux S, et al. Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses. Blood. 2009;113:3716–25.

    Article  CAS  Google Scholar 

  10. Roederer M, Quaye L, Mangino M, Beddall MH, Mahnke Y, Chattopadhyay P, et al. The genetic architecture of the human immune system: a bioresource for autoimmunity and disease pathogenesis. Cell. 2015;161:387–403.

    Article  CAS  Google Scholar 

  11. Forthal DN, Landucci G, Bream J, Jacobson LP, Phan TB, Montoya B. FcgammaRIIa genotype predicts progression of HIV infection. J Immunol. 2007;179:7916–23.

    Article  CAS  Google Scholar 

  12. Geraghty DE, Thorball CW, Fellay J, Thomas R. Effect of Fc receptor genetic diversity on HIV-1 disease pathogenesis. Front Immunol. 2019;10:970.

    Article  CAS  Google Scholar 

  13. Li SS, Gilbert PB, Tomaras GD, Kijak G, Ferrari G, Thomas R, et al. FCGR2C polymorphisms associate with HIV-1 vaccine protection in RV144 trial. J Clin Investig. 2014;124:3879–90.

    Article  CAS  Google Scholar 

  14. Li SS, Gilbert PB, Carpp LN, Pyo CW, Janes H, Fong Y, et al. Fc gamma receptor polymorphisms modulated the vaccine effect on HIV-1 risk in the HVTN 505 HIV vaccine trial. J Virol. 2019;93:e02041–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Deepe RN, Kistner-Griffin E, Martin JN, Deeks SG, Pandey JP. Epistatic interactions between Fc (GM) and FcgammaR genes and the host control of human immunodeficiency virus replication. Hum Immunol. 2012;73:263–6.

    Article  CAS  Google Scholar 

  16. Okulicz JF, Lambotte O. Epidemiology and clinical characteristics of elite controllers. Curr Opin HIV AIDS. 2011;6:163–8.

    Article  Google Scholar 

  17. Lecuroux C, Saez-Cirion A, Girault I, Versmisse P, Boufassa F, Avettand-Fenoel V, et al. Both HLA-B*57 and plasma HIV RNA levels contribute to the HIV-specific CD8+ T cell response in HIV controllers. J Virol. 2014;88:176–87.

    Article  Google Scholar 

  18. Scully EP. Sex differences in HIV infection. Curr HIV/AIDS Rep. 2018;15:136–46.

    Article  Google Scholar 

  19. Willcocks LC, Carr EJ, Niederer HA, Rayner TF, Williams TN, Yang W, et al. A defunctioning polymorphism in FCGR2B is associated with protection against malaria but susceptibility to systemic lupus erythematosus. Proc Natl Acad Sci USA. 2010;107:7881–5.

    Article  CAS  Google Scholar 

  20. McLaren PJ, Coulonges C, Bartha I, Lenz TL, Deutsch AJ, Bashirova A, et al. Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load. Proc Natl Acad Sci USA. 2015;112:14658–63.

    Article  CAS  Google Scholar 

  21. Hespel C, Moser M. Role of inflammatory dendritic cells in innate and adaptive immunity. Eur J Immunol. 2012;42:2535–43.

    Article  CAS  Google Scholar 

Download references

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).

Author information

Authors and Affiliations

  1. Université de Strasbourg, Laboratoire d’ImmunoRhumatologie Moléculaire, INSERM UMR_S 1109, Faculté de Médecine, plateforme GENOMAX, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), LabEx TRANSPLANTEX, Université de Strasbourg, 4 rue Kirschleger, 67085, Strasbourg, France

    Raphael Carapito, Luzia Mayr, Anne Molitor, Martin Verniquet, Sylvie Schmidt, Ouria Tahar, Seiamak Bahram & Christiane Moog

  2. Service d’Immunologie Biologique, Plateau Technique de Biologie, Pôle de Biologie, Nouvel Hôpital Civil, 1 place de l’Hôpital, 67091, Strasbourg, France

    Raphael Carapito, Ouria Tahar & Seiamak Bahram

  3. Le Trait d’Union—NHC, Centre de soins de l’infection par le VIH, Hôpitaux Universitaires de Strasbourg, Strasbourg, France

    Marialuisa Partisani & David Rey

  4. Centre de Recherche en Immunologie des Infections Virales et des Maladies Auto-immunes, Université Paris-Saclay, INSERM, CEA, 94270, Le Kremlin Bicêtre, France

    Olivier Lambotte

  5. AP-HP, Service de Médecine Interne/Immunologie Clinique, Hôpital Bicêtre, Université Paris-Saclay, 94270, Le Kremlin Bicêtre, France

    Olivier Lambotte

  6. Vaccine Research Institute (VRI), Créteil, France

    Christiane Moog

Authors
  1. Raphael Carapito
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luzia Mayr
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anne Molitor
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Martin Verniquet
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sylvie Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ouria Tahar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marialuisa Partisani
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. David Rey
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Olivier Lambotte
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Seiamak Bahram
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Christiane Moog
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Raphael Carapito or Christiane Moog.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41435-020-0106-8

This article is cited by

Search

Advanced search

Quick links