Article Text

PDF
Association between a polymorphism in the human programmed death-1 (PD-1) gene and cytomegalovirus infection after kidney transplantation
  1. Thomas W Hoffmann1,2,
  2. Jean-Michel Halimi1,2,3,
  3. Mathias Büchler1,2,3,
  4. Florence Velge-Roussel1,2,
  5. Alain Goudeau4,
  6. Azmi Al-Najjar3,
  7. Jean-Frédéric Marliere3,
  8. Yvon Lebranchu1,2,3,
  9. Christophe Baron1,2,3
  1. 1Université François Rabelais de Tours, EA 4245 Cellules Dendritiques Immunomodulation et Greffes, UFR de Médecine, Tours, France
  2. 2IFR 136, Infectiologie et Vaccinologie, Tours, France
  3. 3CHRU de Tours, Service de Néphrologie et Immunologie Clinique, Tours, France
  4. 4CHRU de Tours, Service de Bactériologie-Virologie, Tours, France
  1. Correspondence to Professor Dr Christophe Baron, Service de Néphrologie et Immunologie Clinique, CHRU de Tours, 37044 Tours cedex 9, France; baron{at}med.univ-tours.fr

Abstract

Background Cytomegalovirus (CMV) infection is the most frequent infectious disease following organ transplantation. Strategies to prevent this infection remain a matter for debate, and discovering genetic risk factors might assist in adapting preventive strategies. By inhibiting IFNγ production, programmed death 1 (PD-1) has a crucial role in anti-CMV immune response. A single nucleotide polymorphism (SNP) within intron 4 of the gene (rs11568821), called PD-1.3, has recently been reported to be clinically relevant in several immune disorders. However, its association with CMV infection has never been reported.

Methods In this study, the risk of CMV infection according to PD-1.3 genotype was investigated in 469 kidney graft recipients transplanted between 1995 and 2005.

Results It was found that the A allele was associated with the risk of CMV infection in seropositive patients who did not receive CMV prophylaxis (OR=2.60, p=0.006). Multivariate analysis including other risk factors for CMV infection showed that this allele was independently associated with CMV infection (OR=2.54; p=0.010). Interestingly, combined analysis of PD-1.3 with the IL12B 3′UTR SNPs (previously shown to be associated with CMV infection) revealed that patients with the PD-1.3 A allele had a much higher risk of CMV infection compared to those having neither risk allele (OR=3.76; p=0.0003).

Conclusion This study identified a new genetic risk factor for CMV infection after kidney transplantation and suggests that an adjustment of CMV prophylaxis based on genetic markers would merit further investigation.

  • Programmed death-1
  • genetic polymorphism
  • cytomegalovirus infection
  • kidney transplantation
  • molecular genetics
  • immunology (including allergy)
  • infectious diseases
  • renal medicine

Statistics from Altmetric.com

Footnotes

  • Funding This work was supported by grants from the Société Francophone de Transplantation and Vaincre La Mucoviscidose.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Ethical Committee of Tours Hospital.

  • Patient consent Obtained.

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

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.