Jérôme Le Pavec1, Caroline Suberbielle2, Lilia Lamrani3, Séverine Feuillet4, Laurent Savale5, Peter Dorfmüller6, François Stephan7, Sacha Mussot4, Olaf Mercier4, Elie Fadel4. 1. 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. 2. Laboratoire d'histocompatibilité, AP-HP, Hôpital Saint Louis, Paris, France. 3. 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. 4. 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. 5. 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. 6. 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. 7. 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.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Early de-novo DSA may significantly impact long-term outcomes after lung transplantation and should therefore prompt regular screening.
BACKGROUND: 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. METHODS: 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. RESULTS: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). CONCLUSION: Early de-novo DSA may significantly impact long-term outcomes after lung transplantation and should therefore prompt regular screening.
Authors: Daniel R Calabrese; Ping Wang; Tiffany Chong; Jonathan Hoover; Jonathan P Singer; Dara Torgerson; Steven R Hays; Jeffrey A Golden; Jasleen Kukreja; Daniel Dugger; Jason D Christie; John R Greenland Journal: JCI Insight Date: 2019-11-14
Authors: Deepak K Nayak; Fangyu Zhou; Min Xu; Jing Huang; Moriya Tsuji; Jinsheng Yu; Ramsey Hachem; Andrew E Gelman; Ross M Bremner; Michael A Smith; Thalachallour Mohanakumar Journal: Sci Transl Med Date: 2017-07-12 Impact factor: 17.956
Authors: Andrew M Courtwright; Severine Cao; Isabelle Wood; Hari R Mallidi; Jared Kawasawa; Anna Moniodis; Julie Ng; Souheil El-Chemaly; Hilary J Goldberg Journal: Ann Am Thorac Soc Date: 2019-09
Authors: Ramsey R Hachem; Malek Kamoun; Marie M Budev; Medhat Askar; Vivek N Ahya; James C Lee; Deborah J Levine; Marilyn S Pollack; Gundeep S Dhillon; David Weill; Kenneth B Schechtman; Lorriana E Leard; Jeffrey A Golden; LeeAnn Baxter-Lowe; Thalachallour Mohanakumar; Dolly B Tyan; Roger D Yusen Journal: Am J Transplant Date: 2018-05-15 Impact factor: 8.086
Authors: A I Dipchand; S Webber; K Mason; B Feingold; C Bentlejewski; W T Mahle; R Shaddy; C Canter; E D Blume; J Lamour; W Zuckerman; H Diop; Y Morrison; B Armstrong; D Ikle; J Odim; A Zeevi Journal: Am J Transplant Date: 2018-03-24 Impact factor: 8.086
Authors: Hrishikesh S Kulkarni; Kevin Tsui; Suraj Sunder; Alex Ganninger; Laneshia K Tague; Chad A Witt; Derek E Byers; Elbert P Trulock; Ruben Nava; Varun Puri; Daniel Kreisel; Thalachallour Mohanakumar; Andrew E Gelman; Ramsey R Hachem Journal: Am J Transplant Date: 2019-12-24 Impact factor: 8.086