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Association between a polymorphism in the human programmed death-1 (PD-1) gene and CMV infection after kidney transplantation
  1. Thomas W Hoffmann (thomas.hoffmann{at}etu.univ-tours.fr)
  1. Université François Rabelais de Tours, France
    1. Jean-Michel Halimi
    1. Université François Rabelais de Tours and CHRU de Tours, France
      1. Mathias Büchler
      1. Université François Rabelais de Tours and CHRU de Tours, France
        1. Florence Velge-Roussel
        1. Université François Rabelais de Tours, France
          1. Alain Goudeau
          1. Université François Rabelais de Tours and CHRU de Tours, France
            1. Azmi Al-Najjar
            1. Université François Rabelais de Tours and CHRU de Tours, France
              1. Jean-Frédéric Marliere
              1. CHRU de Tours, France
                1. Yvon Lebranchu
                1. Université François Rabelais de Tours and CHRU de Tours, France
                  1. Christophe Baron (baron{at}med.univ-tours.fr)
                  1. Université François Rabelais de Tours and CHRU de Tours, France

                    Abstract

                    Background: Cytomegalovirus (CMV) infection is the most frequent infectious disease following organ transplantation. Strategies to prevent this infection remain matter of 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 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, we investigated the risk of CMV infection according to PD-1.3 genotype in 469 kidney graft recipients transplanted between 1995 and 2005.

                    Results: We 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.

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