Maxim Durand1, Philippe Lacoste2, Richard Danger3, Lola Jacquemont3, Carole Brosseau3, Eugénie Durand3, Gaelle Tilly3, Jennifer Loy2, Aurore Foureau2, Pierre-Joseph Royer2, Adrien Tissot4, Antoine Roux5, Martine Reynaud-Gaubert6, Romain Kessler7, Sacha Mussot8, Claire Dromer9, Olivier Brugière10, Jean François Mornex11, Romain Guillemain12, Johanna Claustre13, Nicolas Degauque3, Antoine Magnan2, Sophie Brouard14. 1. Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France; Institut de Transplantation Urologie Néphrologie, CHU Nantes, Nantes, France; Faculté de Médecine, Université de Nantes, Nantes, France. 2. Institut du thorax, Inserm UMR 1087, CNRS UMR 6291, Université de Nantes, Nantes, France; Institut du thorax, CHU de Nantes, Nantes, France. 3. Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France; Institut de Transplantation Urologie Néphrologie, CHU Nantes, Nantes, France. 4. Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France; Institut de Transplantation Urologie Néphrologie, CHU Nantes, Nantes, France; Faculté de Médecine, Université de Nantes, Nantes, France; Institut du thorax, Inserm UMR 1087, CNRS UMR 6291, Université de Nantes, Nantes, France; Institut du thorax, CHU de Nantes, Nantes, France. 5. Hôpital Foch, Suresnes, Université de Versailles, Saint-Quentin-en-Yvelines, France. 6. CHU de Marseille, Aix Marseille Université, Marseille, France. 7. CHU de Strasbourg, Strasbourg, France. 8. Centre Chirurgical Marie Lannelongue, Service de Chirurgie Thoracique, Vasculaire et Transplantation Cardiopulmonaire, Le Plessis Robinson, France. 9. CHU de Bordeaux, Bordeaux, France. 10. Hôpital Bichat, Service de Pneumologie et Transplantation Pulmonaire, Paris, France. 11. Université de Lyon, INRA, UMR 754, Lyon, Hospices Civils de Lyon, Lyon, France. 12. Hôpital Européen George Pompidou, Paris, France. 13. Clinique Universitaire de Pneumologie, Pôle Thorax et Vaisseaux, CHU Grenoble Alpes, Université Grenoble Alpes, Inserm U1055, Grenoble, France. 14. Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France; Institut de Transplantation Urologie Néphrologie, CHU Nantes, Nantes, France; Centre d'Investigation Clinique Biothérapie, CHU Nantes, Nantes, France. Electronic address: sophie.brouard@univ-nantes.fr.
Abstract
BACKGROUND: Chronic bronchiolitis obliterans syndrome (BOS) remains a major limitation for long-term survival after lung transplantation. The immune mechanisms involved and predictive biomarkers have yet to be identified. The purpose of this study was to determine whether peripheral blood T-lymphocyte profile could predict BOS in lung transplant recipients. METHODS: An in-depth profiling of CD4+ and CD8+ T cells was prospectively performed on blood cells from stable (STA) and BOS patients with a longitudinal follow-up. Samples were analyzed at 1 and 6 months after transplantation, at the time of BOS diagnosis, and at an intermediate time-point at 6 to 12 months before BOS diagnosis. RESULTS: Although no significant difference was found for T-cell compartments at BOS diagnosis or several months beforehand, we identified an increase in the CD4+CD25hiFoxP3+ T-cell sub-population in BOS patients at 1 and 6 months after transplantation (3.39 ± 0.40% vs 1.67 ± 0.22% in STA, p < 0.001). A CD4+CD25hiFoxP3+ T-cell threshold of 2.4% discriminated BOS and stable patients at 1 month post-transplantation. This was validated on a second set of patients at 6 months post-transplantation. Patients with a proportion of CD4+CD25hiFoxP3+ T cells up to 2.4% in the 6 months after transplantation had a 2-fold higher risk of developing BOS. CONCLUSIONS: This study is the first to report an increased proportion of circulating CD4+CD25hiFoxP3+ T cells early post-transplantation in lung recipients who proceed to develop BOS within 3 years, which supports its use as a BOS predictive biomarker.
BACKGROUND:Chronic bronchiolitis obliterans syndrome (BOS) remains a major limitation for long-term survival after lung transplantation. The immune mechanisms involved and predictive biomarkers have yet to be identified. The purpose of this study was to determine whether peripheral blood T-lymphocyte profile could predict BOS in lung transplant recipients. METHODS: An in-depth profiling of CD4+ and CD8+ T cells was prospectively performed on blood cells from stable (STA) and BOSpatients with a longitudinal follow-up. Samples were analyzed at 1 and 6 months after transplantation, at the time of BOS diagnosis, and at an intermediate time-point at 6 to 12 months before BOS diagnosis. RESULTS: Although no significant difference was found for T-cell compartments at BOS diagnosis or several months beforehand, we identified an increase in the CD4+CD25hiFoxP3+ T-cell sub-population in BOSpatients at 1 and 6 months after transplantation (3.39 ± 0.40% vs 1.67 ± 0.22% in STA, p < 0.001). A CD4+CD25hiFoxP3+ T-cell threshold of 2.4% discriminated BOS and stable patients at 1 month post-transplantation. This was validated on a second set of patients at 6 months post-transplantation. Patients with a proportion of CD4+CD25hiFoxP3+ T cells up to 2.4% in the 6 months after transplantation had a 2-fold higher risk of developing BOS. CONCLUSIONS: This study is the first to report an increased proportion of circulating CD4+CD25hiFoxP3+ T cells early post-transplantation in lung recipients who proceed to develop BOS within 3 years, which supports its use as a BOS predictive biomarker.
Authors: Eric D Morrell; Carolyn Brager; Kathleen J Ramos; Xin-Ya Chai; Siddhartha G Kapnadak; Jeffrey Edelman; Gustavo Matute-Bello; William A Altemeier; Billanna Hwang; Michael S Mulligan; Pavan K Bhatraju; Mark M Wurfel; Carmen Mikacenic; Erika D Lease; Ajit P Limaye; Cynthia E Fisher Journal: Am J Respir Cell Mol Biol Date: 2022-05 Impact factor: 6.914