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 - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Frontiers in Medicine Année : 2023

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

1 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
2 Institut du Thorax [Nantes]
3 U1064 Inserm - CR2TI - Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
4 Team 4 - U1064 Inserm - CR2TI - Team 4 : Deciphering organ immune regulation in inflammation and transplantation (DORI-t)
5 ITERT - Institut de Transplantation et de Recherche en Transplantation [CHU Nantes]
6 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
7 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
8 VIM (UR 0892) - Virologie et Immunologie Moléculaires
9 Service de pneumologie [Hôpital Foch]
10 MEPHI - Microbes évolution phylogénie et infections
11 IHU Marseille - Institut Hospitalier Universitaire Méditerranée Infection
12 Hôpital Nord [CHU - APHM]
13 HUS - Les Hôpitaux Universitaires de Strasbourg
14 NanoRegMed - Nanomédecine Régénérative
15 Hôpital Marie-Lannelongue
16 PHERE (UMR_S_1152 / U1152) - Physiopathologie et Epidémiologie des Maladies Respiratoires
17 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
18 Hôpital Haut-Lévêque [CHU Bordeaux]
19 UT3 - Université Toulouse III - Paul Sabatier
20 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
21 IVPC - Infections Virales et Pathologie Comparée - UMR 754
22 LIT - Laboratoire d'Innovation Thérapeutique
23 Monash University [Melbourne]
24 EISBM - European Institute for Systems Biology and Medicine [Vourles]
25 Hôpital Foch [Suresnes]

Résumé

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.
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inserm-04192051 , version 1 (31-08-2023)

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Christophe Pison, Adrien Tissot, Eric Bernasconi, Pierre-Joseph Royer, Antoine Roux, et al.. 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. Frontiers in Medicine, 2023, 10, pp.1126697. ⟨10.3389/fmed.2023.1126697⟩. ⟨inserm-04192051⟩
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