Systems prediction of chronic lung allograft dysfunction: Results and perspectives from the Cohort of Lung Transplantation and Systems prediction of Chronic Lung Allograft Dysfunction cohorts.

Autor:	Pison C; Service Hospitalier Universitaire de Pneumologie Physiologie, Pôle Thorax et Vaisseaux, Fédération Grenoble Transplantation, CHU Grenoble Alpes, Grenoble, France.; Université Grenoble Alpes, INSERM 1055, Grenoble, France., Tissot A; Service de Pneumologie, Institut du Thorax, CHU Nantes, Nantes, France.; CHU Nantes, Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology (CR2TI), UMR 1064, ITUN, Nantes, France., Bernasconi E; Unité de Transplantation Pulmonaire, Service de Pneumologie, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Suisse., Royer PJ; CHU Nantes, Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology (CR2TI), UMR 1064, ITUN, Nantes, France., Roux A; Service de Pneumologie, Hôpital Foch, Suresnes, France.; Institut National de Recherche Pour l'Agriculture, l'Alimentation et l'Environnement, INRAE, Jouy-en-Josas, France., Koutsokera A; Unité de Transplantation Pulmonaire, Service de Pneumologie, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Suisse., Coiffard B; Service de Pneumologie et de Transplantation Pulmonaire, APHM, Hôpital Nord, Aix Marseille Univ, Marseille, France., Renaud-Picard B; Service de Pneumologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.; Inserm UMR 1260, Regenerative Nanomedicine, Université de Strasbourg, Strasbourg, France., Le Pavec J; Service de Chirurgie Thoracique, Vasculaire et Transplantation Cardiopulmonaire, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France., Mordant P; Service de Chirurgie Vasculaire, Thoracique et Transplantation Pulmonaire, Hôpital Bichat, AP-HP, INSERM U1152, Université Paris Cité, Paris, France., Demant X; Service de Pneumologie et Transplantation Pulmonaire, CHU de Bordeaux, Bordeaux, France., Villeneuve T; Service de Pneumologie, CHU de Toulouse, Université Toulouse III-Paul Sabatier, Toulouse, France., Mornex JF; Université de Lyon, Université Lyon 1, PSL, EPHE, INRAE, IVPC, Lyon, France.; Hospices Civils de Lyon, GHE, Service de Pneumologie, RESPIFIL, Orphalung, Inserm CIC, Lyon, France., Nemska S; UMR 7200 - Laboratoire d'Innovation Thérapeutique, Faculté de Pharmacie, CNRS-Université de Strasbourg, Illkirch, France., Frossard N; UMR 7200 - Laboratoire d'Innovation Thérapeutique, Faculté de Pharmacie, CNRS-Université de Strasbourg, Illkirch, France., Brugière O; Service de Pneumologie, Hôpital Foch, Suresnes, France.; Laboratoire d'Immunologie de la Transplantation, Hôpital Saint-Louis, CEA/DRF/Institut de Biologie François Jacob, Unité INSERM 1152, Université Paris Diderot, USPC, Paris, France., Siroux V; Team of Environmental Epidemiology Applied to the Development and Respiratory Health, Institute for Advanced Biosciences (IAB), Inserm U1209, CNRS UMR 5309, Université Grenoble Alpes, Grenoble, France., Marsland BJ; Unité de Transplantation Pulmonaire, Service de Pneumologie, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Suisse.; Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC, Australia., Foureau A; Service de Pneumologie, Institut du Thorax, CHU Nantes, Nantes, France.; CHU Nantes, Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology (CR2TI), UMR 1064, ITUN, Nantes, France., Botturi K; CHU Nantes, Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology (CR2TI), UMR 1064, ITUN, Nantes, France., Durand E; CHU Nantes, Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology (CR2TI), UMR 1064, ITUN, Nantes, France., Pellet J; European Institute for Systems Biology and Medicine, Vourles, France., Danger R; CHU Nantes, Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology (CR2TI), UMR 1064, ITUN, Nantes, France., Auffray C; European Institute for Systems Biology and Medicine, Vourles, France., Brouard S; CHU Nantes, Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology (CR2TI), UMR 1064, ITUN, Nantes, France., Nicod L; Unité de Transplantation Pulmonaire, Service de Pneumologie, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Suisse., Magnan A; Service de Pneumologie, Hôpital Foch, Suresnes, France.; Institut National de Recherche Pour l'Agriculture, l'Alimentation et l'Environnement, INRAE, Jouy-en-Josas, France.
Jazyk:	angličtina
Zdroj:	Frontiers in medicine [Front Med (Lausanne)] 2023 Mar 09; Vol. 10, pp. 1126697. Date of Electronic Publication: 2023 Mar 09 (Print Publication: 2023).
DOI:	10.3389/fmed.2023.1126697
Abstrakt:	Background: Chronic lung allograft dysfunction (CLAD) is the leading cause of poor long-term survival after lung transplantation (LT). Systems prediction of Chronic Lung Allograft Dysfunction (SysCLAD) aimed to predict CLAD. Methods: To predict CLAD, we investigated the clinicome of patients with LT; the exposome through assessment of airway microbiota in bronchoalveolar lavage cells and air pollution studies; the immunome with works on activation of dendritic cells, the role of T cells to promote the secretion of matrix metalloproteinase-9, and subpopulations of T and B cells; genome polymorphisms; blood transcriptome; plasma proteome studies and assessment of MSK1 expression. Results: Clinicome: the best multivariate logistic regression analysis model for early-onset CLAD in 422 LT eligible patients generated a ROC curve with an area under the curve of 0.77. Exposome: chronic exposure to air pollutants appears deleterious on lung function levels in LT recipients (LTRs), might be modified by macrolides, and increases mortality. Our findings established a link between the lung microbial ecosystem, human lung function, and clinical stability post-transplant. Immunome: a decreased expression of CLEC1A in human lung transplants is predictive of the development of chronic rejection and associated with a higher level of interleukin 17A; Immune cells support airway remodeling through the production of plasma MMP-9 levels, a potential predictive biomarker of CLAD. Blood CD9-expressing B cells appear to favor the maintenance of long-term stable graft function and are a potential new predictive biomarker of BOS-free survival. An early increase of blood CD4 + CD57 + ILT2+ T cells after LT may be associated with CLAD onset. Genome: Donor Club cell secretory protein G38A polymorphism is associated with a decreased risk of severe primary graft dysfunction after LT. Transcriptome: blood POU class 2 associating factor 1, T-cell leukemia/lymphoma domain, and B cell lymphocytes, were validated as predictive biomarkers of CLAD phenotypes more than 6 months before diagnosis. Proteome: blood A2MG is an independent predictor of CLAD, and MSK1 kinase overexpression is either a marker or a potential therapeutic target in CLAD. Conclusion: Systems prediction of Chronic Lung Allograft Dysfunction generated multiple fingerprints that enabled the development of predictors of CLAD. These results open the way to the integration of these fingerprints into a predictive handprint. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Pison, Tissot, Bernasconi, Royer, Roux, Koutsokera, Coiffard, Renaud-Picard, Le Pavec, Mordant, Demant, Villeneuve, Mornex, Nemska, Frossard, Brugière, Siroux, Marsland, Foureau, Botturi, Durand, Pellet, Danger, Auffray, Brouard, Nicod, Magnan and Members of the COhort of Lung Transplantation and Systems prediction of Chronic Lung Allograft Dysfunction consortia.)
Databáze:	MEDLINE
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