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Systemic antibody responses to gut commensal bacteria during chronic HIV-1 infection
  1. Anna Haas1,
  2. Kathrin Zimmermann1,
  3. Frederik Graw2,
  4. Emma Slack3,
  5. Peter Rusert4,
  6. Bruno Ledergerber5,
  7. Walter Bossart4,
  8. Rainer Weber5,
  9. Maria C Thurnheer6,
  10. Manuel Battegay7,
  11. Bernard Hirschel8,
  12. Pietro Vernazza9,
  13. Nicola Patuto3,
  14. Andrew J Macpherson3,
  15. Huldrych F Günthard5,
  16. Annette Oxenius1,
  17. the Swiss HIV Cohort Study*
  1. 1Institute of Microbiology, ETH Zurich, Zurich, Switzerland
  2. 2Institute of Integrative Biology, ETH Zurich, Zurich, Switzerland
  3. 3Gastroenterology, University Hospital Bern, University of Bern, Bern, Switzerland
  4. 4Institute of Medical Virology, University of Zurich, Zurich, Switzerland
  5. 5Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
  6. 6Division of Infectious Diseases, University Hospital Bern, University of Bern, Switzerland
  7. 7Division of Infectious Diseases and Hospital Epidemiology, University of Basel, Basel, Switzerland
  8. 8Division of Infectious Diseases, University Hospital Lausanne, Lausanne, Switzerland
  9. 9Division of Infectious Diseases, Kantonsspital St. Gallen, St. Gallen, Switzerland
  1. Correspondence to Annette Oxenius, Institute of Microbiology, ETH Zurich, Wolfgang-Pauli-Str. 10, HCI G401, 8093 Zurich, Switzerland; oxenius{at}micro.biol.ethz.ch

Abstract

Background Human systemic antibody responses to commensal microbiota are not well characterised during health and disease. Of particular interest is the analysis of their potential modulation caused by chronic HIV-1 infection which is associated with sustained enteropathy and systemic B cell disturbances reflected by impaired B cell responses and chronic B cell hyperactivity. The mechanisms underlying B cell hyperactivation and the specificities of the resulting hypergammaglobulinaemia are only poorly understood.

Methods By a technique referred to as live bacterial FACS (fluorescence-activated cell sorting), the present study investigated systemic antibody responses to several gut and skin commensal bacteria as well as Candida albicans in longitudinal plasma and serum samples from healthy donors, chronic HIV-1-infected individuals with or without diarrhoea and patients with inflammatory bowel disease (IBD).

Results The data show that systemic antibody responses to the commensal microbiota were abundantly present in humans and remained remarkably stable over years. Overall systemic antibody responses to gut commensal bacteria were not affected during chronic HIV-1 infection, with titres decreasing when normalised to elevated plasma immunoglobulin G (IgG) levels found in patients with HIV. In contrast, increases in the titres of high affinity antimicrobiota antibodies were detected in patients with IBD, demonstrating that conditions with known increased intestinal permeability and aberrant mutualism can induce changes in antibody titres observed in these assays.

Conclusion Neither HIV-associated enteropathy nor B cell dysfunction impact on the high-affinity systemic antibody responses to gut commensal bacteria. HIV-associated hypergammaglobulinaemia is therefore unlikely to be driven by induction of antimicrobiota antibodies.

  • HIV enteropathy
  • hypergammaglobulinaemia
  • microbiota
  • bacterial translocation
  • antibody responses
  • B cell
  • bacterial translocation
  • HIV-related gastrointestinal disease
  • hypogammaglobulinaemia
  • intestinal bacteria

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Footnotes

  • * The members of the Swiss HIV Cohort Study and the Swiss Mother and Child HIV Study are: Barth J, Battegay M, Bernasconi E, Böni J (SNF-grant 315200-114148), Brazzola P, Bucher HC, Bürgisser P, Burton-Jeangros C, Calmy A, Cavassini M, Cheseaux JJ, Drack G, Dubs R, Duppenthaler A, Egger M, Elzi L, Fehr J, Fischer M, Flepp M, Francioli P (President of the SHCS), Furrer H, Fux CA, Gorgievski M, Grawe C, Günthard H, Gyr T, Hasse B, Hirsch HH, Hirschel B, Hösli I, Kahlert C, Kaiser L, Keiser O, Kind C, Klimkait T, Kovari H, Ledergerber B, Martinetti G, Martinez de Tejada B, Müller N, Nadal D, Pantaleo G, Posfay-Barbe K, Raio L, Rauch A, Regenass S, Rickenbach M, Rudin C (Chairman of the Mother & Child Substudy), Schmid P, Schultze D, Schöni-Affolter F, Schüpbach J, Speck R, Taffé P, Telenti A, Trkola A, Vernazza P, von Wyl V, Weber R, Wyler CA, Yerly S.

  • Funding This work was supported by the Swiss National Science Foundation (grant # 310000-129751 to AO, grant # 130865 to HFG and grant # 315200-114148 to Roland Regoes), and by the SHCS project No 598. The SHCS is financed in the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (SNF grant #3345-062041).

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the University Hospital Zurich and the University Hospital Bern.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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