Blood Gene Expression Predicts Bronchiolitis Obliterans Syndrome.

Autor: Danger R; Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.; Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France., Royer PJ; UMR S 1087 CNRS UMR 6291, l'Institut du Thorax, Université de Nantes, CHU Nantes, Nantes, France., Reboulleau D; UMR S 1087 CNRS UMR 6291, l'Institut du Thorax, Université de Nantes, CHU Nantes, Nantes, France., Durand E; UMR S 1087 CNRS UMR 6291, l'Institut du Thorax, Université de Nantes, CHU Nantes, Nantes, France., Loy J; UMR S 1087 CNRS UMR 6291, l'Institut du Thorax, Université de Nantes, CHU Nantes, Nantes, France., Tissot A; Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.; UMR S 1087 CNRS UMR 6291, l'Institut du Thorax, Université de Nantes, CHU Nantes, Nantes, France., Lacoste P; UMR S 1087 CNRS UMR 6291, l'Institut du Thorax, Université de Nantes, CHU Nantes, Nantes, France., Roux A; Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes, France.; Universite Versailles Saint-Quentin-en-Yvelines, UPRES EA220, Suresnes, France., Reynaud-Gaubert M; Service de Pneumologie et Transplantation Pulmonaire, CHU Nord de Marseille, Aix-Marseille Université, Marseille, France., Gomez C; Service de Pneumologie et Transplantation Pulmonaire, CHU Nord de Marseille, Aix-Marseille Université, Marseille, France., Kessler R; Groupe de Transplantation Pulmonaire des Hôpitaux universitaires de Strasbourg, Strasbourg, France., Mussot S; Hôpital Marie Lannelongue, Service de Chirurgie Thoracique, Vasculaire et Transplantation Cardiopulmonaire, Le Plessis Robinson, France., Dromer C; CHU de Bordeaux, Bordeaux, France., Brugière O; Hôpital Bichat, Service de Pneumologie et Transplantation Pulmonaire, Paris, France., Mornex JF; Université de Lyon, INRA, UMR754, Lyon, Hospices Civils de Lyon, Lyon, France., Guillemain R; Hôpital Européen George Pompidou, Paris, France., Dahan M; CHU de Toulouse, Toulouse, France., Knoop C; Hôpital Erasme, Bruxelles, Belgique., Botturi K; UMR S 1087 CNRS UMR 6291, l'Institut du Thorax, Université de Nantes, CHU Nantes, Nantes, France., Foureau A; UMR S 1087 CNRS UMR 6291, l'Institut du Thorax, Université de Nantes, CHU Nantes, Nantes, France., Pison C; Clinique Universitaire Pneumologie, Pôle Thorax et Vaisseaux, CHU de Grenoble, Université de Grenoble, INSERM U1055, Grenoble, France., Koutsokera A; Service de Pneumologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland., Nicod LP; Service de Pneumologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland., Brouard S; Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.; Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France., Magnan A; UMR S 1087 CNRS UMR 6291, l'Institut du Thorax, Université de Nantes, CHU Nantes, Nantes, France.
Jazyk: angličtina
Zdroj: Frontiers in immunology [Front Immunol] 2018 Jan 11; Vol. 8, pp. 1841. Date of Electronic Publication: 2018 Jan 11 (Print Publication: 2017).
DOI: 10.3389/fimmu.2017.01841
Abstrakt: Bronchiolitis obliterans syndrome (BOS), the main manifestation of chronic lung allograft dysfunction, leads to poor long-term survival after lung transplantation. Identifying predictors of BOS is essential to prevent the progression of dysfunction before irreversible damage occurs. By using a large set of 107 samples from lung recipients, we performed microarray gene expression profiling of whole blood to identify early biomarkers of BOS, including samples from 49 patients with stable function for at least 3 years, 32 samples collected at least 6 months before BOS diagnosis (prediction group), and 26 samples at or after BOS diagnosis (diagnosis group). An independent set from 25 lung recipients was used for validation by quantitative PCR (13 stables, 11 in the prediction group, and 8 in the diagnosis group). We identified 50 transcripts differentially expressed between stable and BOS recipients. Three genes, namely POU class 2 associating factor 1 ( POU2AF1 ), T-cell leukemia/lymphoma protein 1A ( TCL1A ), and B cell lymphocyte kinase, were validated as predictive biomarkers of BOS more than 6 months before diagnosis, with areas under the curve of 0.83, 0.77, and 0.78 respectively. These genes allow stratification based on BOS risk (log-rank test p  < 0.01) and are not associated with time posttransplantation. This is the first published large-scale gene expression analysis of blood after lung transplantation. The three-gene blood signature could provide clinicians with new tools to improve follow-up and adapt treatment of patients likely to develop BOS.
Databáze: MEDLINE
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