title: De-novo donor-specific anti-HLA antibodies 30 days after lung transplantation are associated with a worse outcome.
abstract: The impact of de-novo donor-specific anti-HLA antibodies (DSA) on patient and graft survival after lung transplantation remains controversial. We analyzed DSA that developed at Day 7 and Month (M) 1, M3, M6 and M12 after lung transplantation and evaluated their impact on chronic lung allograft dysfunction (CLAD) development and survival.
  
  
  
  One hundred thirty-four patients who underwent lung transplantation at our institution between November 2007 and August 2013 were included in this study. During the first post-transplant year, 82 (61%) patients developed de novo DSA and 52 (39%) patients did not. Three mean fluorescence intensity (MFI) intervals were used to define scores of anti-HLA antibody positivity: score 4 if MFI was 500 to 1,000; score 6 if MFI was 1,000 to 3,000; and score 8 if MFI was ≥3,000. Patients' records were retrospectively reviewed.
  
  
  
  DSA with MFI scores of ≥4 (hazard ratio [HR] 2.21, 95% confidence interval [CI] 1.08 to 4.54, p = 0.03), 6 (HR 2.63, 95% CI 1.27 to 5.20, p < 0.01) and 8 (HR 2.83, 95% CI 1.42 to 5.67, p < 0.01) at M1; female gender (HR 0.49, 95% CI 0.28 to 0.87, P = 0.01); and with post-operative extracorporeal membrane oxygenation (HR 0.09, 95% CI 0.01 to 0.28, p = 0.02) were significantly associated with CLAD. Multivariate analysis identified score 8 at M1 (HR 2.71, 95% CI 1.34 to 5.47, p < 0.01) as an independent risk factor for mortality. Overall, 1-, 3- and 5-year survival rates were 76%, 52% and 41% compared with 84%, 74% and 70% for patients with or without de-novo DSA at M1, respectively (p = 0.02).
  
  
  
  Early de-novo DSA may significantly impact long-term outcomes after lung transplantation and should therefore prompt regular screening.
authors.affiliation: Université Paris-Sud, Faculté de Médecine, Université Paris Saclay, Le Kremlin Bicêtre, France; Service de Chirurgie Thoracique, Vasculaire et Transplantation Cardio-pulmonaire, Hôpital Marie-Lannelongue, Le Plessis-Robinson, France; UMR-S 999, Universitaire Paris-Sud, INSERM, Hôpital Marie Lannelongue, Le Plessis Robinson, France. Electronic address: lepavec@gmail.com.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Le Pavec
authors.affiliation: Laboratoire d'histocompatibilité, AP-HP, Hôpital Saint Louis, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Suberbielle
authors.affiliation: Université Paris-Sud, Faculté de Médecine, Université Paris Saclay, Le Kremlin Bicêtre, France; UMR-S 999, Universitaire Paris-Sud, INSERM, Hôpital Marie Lannelongue, Le Plessis Robinson, France.
authors.forename: Lilia
authors.initials: L
authors.lastname: Lamrani
authors.affiliation: Université Paris-Sud, Faculté de Médecine, Université Paris Saclay, Le Kremlin Bicêtre, France; Service de Chirurgie Thoracique, Vasculaire et Transplantation Cardio-pulmonaire, Hôpital Marie-Lannelongue, Le Plessis-Robinson, France; UMR-S 999, Universitaire Paris-Sud, INSERM, Hôpital Marie Lannelongue, Le Plessis Robinson, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Feuillet
authors.affiliation: Université Paris-Sud, Faculté de Médecine, Université Paris Saclay, Le Kremlin Bicêtre, France; UMR-S 999, Universitaire Paris-Sud, INSERM, Hôpital Marie Lannelongue, Le Plessis Robinson, France; AP-HP, Service de Pneumologie, Hôpital de Bicêtre, Le Kremlin Bicêtre, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Savale
authors.affiliation: Université Paris-Sud, Faculté de Médecine, Université Paris Saclay, Le Kremlin Bicêtre, France; UMR-S 999, Universitaire Paris-Sud, INSERM, Hôpital Marie Lannelongue, Le Plessis Robinson, France; Service d'Anatomie Pathologique, Hôpital Marie Lannelongue, Le Plessis-Robinson, France.
authors.forename: Peter
authors.initials: P
authors.lastname: Dorfmüller
authors.affiliation: Université Paris-Sud, Faculté de Médecine, Université Paris Saclay, Le Kremlin Bicêtre, France; UMR-S 999, Universitaire Paris-Sud, INSERM, Hôpital Marie Lannelongue, Le Plessis Robinson, France; Service de Réanimation, Hôpital Marie Lannelongue, Le Plessis-Robinson, France.
authors.forename: François
authors.initials: F
authors.lastname: Stephan
authors.affiliation: Université Paris-Sud, Faculté de Médecine, Université Paris Saclay, Le Kremlin Bicêtre, France; Service de Chirurgie Thoracique, Vasculaire et Transplantation Cardio-pulmonaire, Hôpital Marie-Lannelongue, Le Plessis-Robinson, France; UMR-S 999, Universitaire Paris-Sud, INSERM, Hôpital Marie Lannelongue, Le Plessis Robinson, France.
authors.forename: Sacha
authors.initials: S
authors.lastname: Mussot
authors.affiliation: Université Paris-Sud, Faculté de Médecine, Université Paris Saclay, Le Kremlin Bicêtre, France; Service de Chirurgie Thoracique, Vasculaire et Transplantation Cardio-pulmonaire, Hôpital Marie-Lannelongue, Le Plessis-Robinson, France; UMR-S 999, Universitaire Paris-Sud, INSERM, Hôpital Marie Lannelongue, Le Plessis Robinson, France.
authors.forename: Olaf
authors.initials: O
authors.lastname: Mercier
authors.affiliation: Université Paris-Sud, Faculté de Médecine, Université Paris Saclay, Le Kremlin Bicêtre, France; Service de Chirurgie Thoracique, Vasculaire et Transplantation Cardio-pulmonaire, Hôpital Marie-Lannelongue, Le Plessis-Robinson, France; UMR-S 999, Universitaire Paris-Sud, INSERM, Hôpital Marie Lannelongue, Le Plessis Robinson, France.
authors.forename: Elie
authors.initials: E
authors.lastname: Fadel
mesh_terms: D000961:Antilymphocyte Serum; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006680:HLA Antigens; D006801:Humans; D007518:Isoantibodies; D016030:Kidney Transplantation; D016040:Lung Transplantation; D015996:Survival Rate; D014019:Tissue Donors
chemical_list: D000961:Antilymphocyte Serum; D006680:HLA Antigens; D007518:Isoantibodies
keywords: antibody mediated rejection; chronic lung allograft dysfunction; de-novo donor-specific antibodies; lung transplantation; survival