Polymorphism in programmed cell death 1 gene is strongly associated with lung and kidney allograft survival in recipients from CMV-positive donors - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue The Journal of Heart and Lung Transplantation Année : 2017

Polymorphism in programmed cell death 1 gene is strongly associated with lung and kidney allograft survival in recipients from CMV-positive donors

Catherine Forconi
  • Fonction : Auteur
Philippe Gatault
Johan Noble
  • Fonction : Auteur
  • PersonId : 1262082
  • IdHAL : noble-johan
Sally Al-Hajj
  • Fonction : Auteur
Thomas Hoffmann
  • Fonction : Auteur
Louis Prat
  • Fonction : Auteur
Caroline Suberbielle
  • Fonction : Auteur
Ihab Kazma
  • Fonction : Auteur

Résumé

BACKGROUND: Cytomegalovirus (CMV) has a role in chronic rejection and graft loss in kidney transplant (KTx) and lung transplant (LTx) recipients. In addition, donor CMV seropositivity is an independent risk factor for renal graft loss. The anti-CMV response might modulate this risk. Expression of programmed cell death 1 (PD-1), a receptor involved in viral-specific T-cell exhaustion, is influenced by a single nucleotide polymorphism called PD-1.3 (wild-type allele G, variant allele A). METHODS: We performed a retrospective study to assess the impact of PD-1.3 on graft outcome in donor CMV seropositive (D+) and donor CMV seronegative (D-) KTx and LTx. We also performed a case-control study to evaluate the anti-CMVpp65 response according to genotype. RESULTS: PD-1.3 was determined in 1,119 KTx and 181 LTx. In 481 D+ KTx, A allele carriers (24%) experienced significantly less graft failure compared with GG carriers (p = 0.001). Multivariate analysis showed that this association was independent of donor and recipient age, acute rejection episodes, and number of human leukocyte antigen mismatches (hazard ratio, 0.381; 95% confidence interval, 0.209-0.696; p = 0.002). Analysis in 85 D+ LTx showed similar results: A allele carriers had better survival (hazard ratio, 0.302; 95% confidence interval, 0.128-0.716; p = 0.006) and greater 6-month forced expiratory volume (71% ± 17% vs 54% ± 16%, p = 0.001). In D- recipients, PD-1.3 did not affect KTx or LTx outcome. Finally, AA recipients had a stronger anti-CMVpp65 T-cell response than matched GG recipients (p = 0.003). CONCLUSIONS: The A variant allele in PD-1.3 single nucleotide polymorphism improved graft survival in kidney and lung transplant recipients receiving grafts from CMV-positive donors.
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Dates et versions

hal-01832950 , version 1 (24-07-2018)

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Catherine Forconi, Philippe Gatault, Elodie Miquelestorena-Standley, Johan Noble, Sally Al-Hajj, et al.. Polymorphism in programmed cell death 1 gene is strongly associated with lung and kidney allograft survival in recipients from CMV-positive donors. The Journal of Heart and Lung Transplantation, 2017, Equipe III, 36 (3), pp.315--324. ⟨10.1016/j.healun.2016.08.014⟩. ⟨hal-01832950⟩
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