title: Polymorphism in programmed cell death 1 gene is strongly associated with lung and kidney allograft survival in recipients from CMV-positive donors.
abstract: 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.
authors.affiliation: EA4245 Cellules Dendritiques, Immunomodulation et Greffes, Université François-Rabelais, Tours.
authors.forename: Catherine
authors.initials: C
authors.lastname: Forconi
authors.affiliation: EA4245 Cellules Dendritiques, Immunomodulation et Greffes, Université François-Rabelais, Tours; Service de Néphrologie et Immunologie Clinique, CHRU Tours, Tours; Laboratory of Immunology, CHRU Tours, Tours. Electronic address: philippe.gatault@univ-tours.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gatault
authors.affiliation: EA4245 Cellules Dendritiques, Immunomodulation et Greffes, Université François-Rabelais, Tours.
authors.forename: Elodie
authors.initials: E
authors.lastname: Miquelestorena-Standley
authors.affiliation: EA4245 Cellules Dendritiques, Immunomodulation et Greffes, Université François-Rabelais, Tours; Service de Néphrologie et Immunologie Clinique, CHRU Tours, Tours.
authors.forename: Johan
authors.initials: J
authors.lastname: Noble
authors.affiliation: EA4245 Cellules Dendritiques, Immunomodulation et Greffes, Université François-Rabelais, Tours.
authors.forename: Sally
authors.initials: S
authors.lastname: Al-Hajj
authors.affiliation: Department of Thoracic Surgery and Lung Transplant, HEGP Hospital, Paris.
authors.forename: Romain
authors.initials: R
authors.lastname: Guillemain
authors.affiliation: Pneumology and Lung Transplant Unit, FOCH Hospital, Suresnes.
authors.forename: Marc
authors.initials: M
authors.lastname: Stern
authors.affiliation: EA4245 Cellules Dendritiques, Immunomodulation et Greffes, Université François-Rabelais, Tours.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoffmann
authors.affiliation: EA4245 Cellules Dendritiques, Immunomodulation et Greffes, Université François-Rabelais, Tours; Service de Néphrologie et Immunologie Clinique, CHRU Tours, Tours.
authors.forename: Louis
authors.initials: L
authors.lastname: Prat
authors.affiliation: Laboratory of Immunology and Histocompatibility, Saint-Louis Hospital, APHP, Paris.
authors.forename: Caroline
authors.initials: C
authors.lastname: Suberbielle
authors.affiliation: Laboratory of Immunology and Histocompatibility, Saint-Louis Hospital, APHP, Paris.
authors.forename: Emeline
authors.initials: E
authors.lastname: Masson
authors.affiliation: Laboratory of Histocompatibility, National Blood Bank, Nantes.
authors.forename: Anne
authors.initials: A
authors.lastname: Cesbron-Gautier
authors.affiliation: Laboratory of Bacteriology and Virology, CHRU de Tours, Tours; INSERM U966, Tours University, Tours.
authors.forename: Catherine
authors.initials: C
authors.lastname: Gaudy-Graffin
authors.affiliation: Laboratory of Bacteriology and Virology, CHRU de Tours, Tours; INSERM U966, Tours University, Tours.
authors.forename: Alain
authors.initials: A
authors.lastname: Goudeau
authors.affiliation: Laboratory of Immunology, CHRU Tours, Tours; CNRS UMR 7292, Genetics, Immunotherapy, Chemistry and Cancer, Tours University, Tours.
authors.forename: Gilles
authors.initials: G
authors.lastname: Thibault
authors.affiliation: EA4245 Cellules Dendritiques, Immunomodulation et Greffes, Université François-Rabelais, Tours.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Ivanes
authors.affiliation: EA4245 Cellules Dendritiques, Immunomodulation et Greffes, Université François-Rabelais, Tours.
authors.forename: Roseline
authors.initials: R
authors.lastname: Guibon
authors.affiliation: EA4245 Cellules Dendritiques, Immunomodulation et Greffes, Université François-Rabelais, Tours.
authors.forename: Ihab
authors.initials: I
authors.lastname: Kazma
authors.affiliation: EA4245 Cellules Dendritiques, Immunomodulation et Greffes, Université François-Rabelais, Tours; Service de Néphrologie et Immunologie Clinique, CHRU Tours, Tours.
authors.forename: Yvon
authors.initials: Y
authors.lastname: Lebranchu
authors.affiliation: EA4245 Cellules Dendritiques, Immunomodulation et Greffes, Université François-Rabelais, Tours; Service de Néphrologie et Immunologie Clinique, CHRU Tours, Tours.
authors.forename: Matthias
authors.initials: M
authors.lastname: Büchler
authors.affiliation: INSERM UMR 915, Institut du Thorax, IRT-UN, Nantes, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Magnan
authors.affiliation: EA4245 Cellules Dendritiques, Immunomodulation et Greffes, Université François-Rabelais, Tours; Service de Néphrologie et Immunologie Clinique, CHRU Tours, Tours.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Halimi
authors.affiliation: EA4245 Cellules Dendritiques, Immunomodulation et Greffes, Université François-Rabelais, Tours.
authors.forename: Christophe
authors.initials: C
authors.lastname: Baron
mesh_terms: D000328:Adult; D060890:B7-H1 Antigen / Q000235:genetics*; D016022:Case-Control Studies; D016001:Confidence Intervals; D003587:Cytomegalovirus / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000175:diagnosis*; D005260:Female; D006084:Graft Rejection / Q000235:genetics*; D006085:Graft Survival; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods; D016040:Lung Transplantation / Q000009:adverse effects / Q000379:methods; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016036:Seroepidemiologic Studies; D014019:Tissue Donors; D066027:Transplant Recipients
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human
keywords: clonal exhaustion; cytomegalovirus; graft survival; kidney transplantation; lung transplantation; polymorphism; programmed cell death 1