title: Systematic analysis of blood cell transcriptome in end-stage chronic respiratory diseases.
abstract: BACKGROUND
  End-stage chronic respiratory diseases (CRD) have systemic consequences, such as weight loss and susceptibility to infection. However the mechanisms of such dysfunctions are as yet poorly explained. We hypothesized that the genes putatively involved in these mechanisms would emerge from a systematic analysis of blood mRNA profiles from pre-transplant patients with cystic fibrosis (CF), pulmonary hypertension (PAH), and chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  Whole blood was first collected from 13 patients with PAH, 23 patients with CF, and 28 Healthy Controls (HC). Microarray results were validated by quantitative PCR on a second and independent group (7PAH, 9CF, and 11HC). Twelve pre-transplant COPD patients were added to validate the common signature shared by patients with CRD for all causes. To further clarify a role for hypoxia in the candidate gene dysregulation, peripheral blood mononuclear cells from HC were analysed for their mRNA profile under hypoxia.
  
  
  RESULTS
  Unsupervised hierarchical clustering allowed the identification of 3 gene signatures related to CRD. One was common to CF and PAH, another specific to CF, and the final one was specific to PAH. With the common signature, we validated T-Cell Factor 7 (TCF-7) and Interleukin 7 Receptor (IL-7R), two genes related to T lymphocyte activation, as being under-expressed. We showed a strong impact of the hypoxia on modulation of TCF-7 and IL-7R expression in PBMCs from HC under hypoxia or PBMCs from CRD. In addition, we identified and validated genes upregulated in PAH or CF, including Lectin Galactoside-binding Soluble 3 and Toll Like Receptor 4, respectively.
  
  
  CONCLUSIONS
  Systematic analysis of blood cell transcriptome in CRD patients identified common and specific signatures relevant to the systemic pathologies. TCF-7 and IL-7R were downregulated whatever the cause of CRD and this could play a role in the higher susceptibility to infection of these patients.
authors.affiliation: UMR_S 1087 CNRS UMR_6291, l'Institut du Thorax, Université de Nantes, CHU de Nantes, Centre National de Référence Mucoviscidose Nantes-Roscoff, Nantes, France; Université de Nantes, Nantes, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Chesné
authors.affiliation: Université de Nantes, Nantes, France; Institut National de la Santé et de la Recherche Médicale INSERM U1064, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Danger
authors.affiliation: UMR_S 1087 CNRS UMR_6291, l'Institut du Thorax, Université de Nantes, CHU de Nantes, Centre National de Référence Mucoviscidose Nantes-Roscoff, Nantes, France; Université de Nantes, Nantes, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Botturi
authors.affiliation: CHU de Marseille, Aix Marseille Université, Marseille, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Reynaud-Gaubert
authors.affiliation: Centre Chirurgical Marie Lannelongue, Service de Chirurgie Thoracique, Vasculaire et Transplantation Cardiopulmonaire, Le Plessis Robinson, France.
authors.forename: Sacha
authors.initials: S
authors.lastname: Mussot
authors.affiliation: Hôpital Foch, Suresnes, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Stern
authors.affiliation: UMR_S 1087 CNRS UMR_6291, l'Institut du Thorax, Université de Nantes, CHU de Nantes, Centre National de Référence Mucoviscidose Nantes-Roscoff, Nantes, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Danner-Boucher
authors.affiliation: Université de Lyon, Lyon, France; Université de Lyon 1, Lyon, France; INRA, UMR_S 754, Lyon, France; Hospices Civils de Lyon, Lyon, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Mornex
authors.affiliation: Clinique Universitaire Pneumologie, CHU de Grenoble, Grenoble, France; Université Joseph Fourier, Grenoble, France; Inserm U1055, Grenoble, France; European Institute of Systems Biology and Medicine, Lyon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Pison
authors.affiliation: CHU de Bordeaux, Bordeaux, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Dromer
authors.affiliation: CHU de Strasbourg, Strasbourg, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Kessler
authors.affiliation: CHU de Toulouse, Toulouse, France.
authors.forename: Marcel
authors.initials: M
authors.lastname: Dahan
authors.affiliation: Hôpital Bichat, Service de Pneumologie B et Transplantation Pulmonaire, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Brugière
authors.affiliation: Centre Chirurgical Marie Lannelongue, Service de Chirurgie Thoracique, Vasculaire et Transplantation Cardiopulmonaire, Le Plessis Robinson, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Le Pavec
authors.affiliation: Université Paris-Sud, Le Kremlin-Bicêtre, France; AP-HP, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Perros
authors.affiliation: Université Paris-Sud, Le Kremlin-Bicêtre, France; AP-HP, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.affiliation: CHU de Marseille, Aix Marseille Université, Marseille, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Gomez
authors.affiliation: Université de Nantes, Nantes, France; Institut National de la Santé et de la Recherche Médicale INSERM U1064, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Brouard
authors.affiliation: UMR_S 1087 CNRS UMR_6291, l'Institut du Thorax, Université de Nantes, CHU de Nantes, Centre National de Référence Mucoviscidose Nantes-Roscoff, Nantes, France; Université de Nantes, Nantes, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Magnan
mesh_terms: D000328:Adult; D001773:Blood Cells / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D015687:Cell Hypoxia; D016000:Cluster Analysis; D003550:Cystic Fibrosis / Q000097:blood / Q000235:genetics / Q000473:pathology; D020869:Gene Expression Profiling; D063990:Gene Ontology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000235:genetics / Q000473:pathology; D008171:Lung Diseases / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000235:genetics; D051822:T Cell Transcription Factor 1 / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D051822:T Cell Transcription Factor 1; C497576:TCF7 protein, human