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PLoS One. 2014 Oct 20;9(10):e109291. doi: 10.1371/journal.pone.0109291. eCollection 2014.

Systematic analysis of blood cell transcriptome in end-stage chronic respiratory diseases.

Collaborators (261)

Antoine M, Jougon J, Velly JF, Rozé H, Blanchard E, Dromer C, Antoine M, Cappello M, Souilamas R, Ruiz M, Sokolow Y, Vanden Eynden F, Van Nooten G, Barvais L, Berré J, Brimioulle S, De Backer D, Créteur J, Engelman E, Huybrechts I, Ickx B, Preiser T, Tuna T, Van Obberghe L, Vancutsem N, Vincent JL, De Vuyst P, Etienne I, Féry F, Jacobs F, Knoop C, Vachiéry JL, Van den Borne P, Wellemans I, Amand G, Collignon L, Giroux M, Arnaud-Crozat E, Bach V, Brichon PY, Chaffanjon P, Chavanon O, de Lambert A, Fleury JP, Guigard S, Hireche K, Pirvu A, Porcu P, Hacini R, Albaladejo P, Allègre C, Anglade D, Bedague D, Bouzat P, Briot E, Carle O, Casez-Brasseur M, Colas D, Dessertaine G, Durand M, Duret J, Fèvre MC, Francony G, Gay S, Marino MR, Oummahan B, Protar D, Rehm D, Robin S, Rossi-Blancher M, Saunier L, Bedouch P, Boignard A, Bouvaist H, Briault A, Camara B, Chanoine S, Dubuc M, Lantuéjoul S, Quêtant S, Maurizi J, Pavèse P, Pison C, Saint-Raymond C, Wion N, Chérion C, Grima R, Jegaden O, Maury JM, Tronc F, Flamens C, Paulus S, Mornex JF, Philit F, Senechal A, Glérant JC, Turquier S, Gamondes D, Chalabresse L, Thivolet-Bejui F, Barnel C, Dubois C, Tiberghien A, Le Pimpec-Barthes F, Bel A, Mordant P, Achouh P, Boussaud V, Guillemain R, Méléard D, Bricourt MO, Cholley B, Pezella V, Adda M, Badier M, Bregeon F, Coltey B, D'Journo XB, Dizier S, Doddoli C, Dufeu N, Dutau H, Forel JM, Gaubert JY, Gomez C, Leone M, Nieves A, Orsini B, Papazian L, Picard LC, Reynaud-Gaubert M, Roch A, Rolain JM, Sampol E, Secq V, Thomas P, Trousse D, Yahyaoui M, Baron O, Lacoste P, Perigaud C, Roussel JC, Danner I, Haloun A, Magnan A, Tissot A, Lepoivre T, Treilhaud M, Botturi-Cavaillès K, Brouard S, Danger R, Loy J, Morisset M, Pain M, Pares S, Reboulleau D, Royer PJ, Dartevelle P, Fadel E, Mussot S, Fabre D, Mercier O, Viard P, François S, Cerrina J, Hervé P, Le Pavec J, Ladurie F, Lamran L, Castier Y, Cerceau P, Francis F, Lesèche G, Allou N, Augustin P, Boudinet S, Desmard M, Dufour G, Montravers P, Brugière O, Dauriat G, Jébrak G, Mal H, Marceau A, Métivier AC, Thabut G, Ilalne B, Falcoz P, Massard G, Santelmo N, Ajob G, Collange O, Helms O, Hentz J, Roche A, Bakouboula B, Degot T, Dory A, Hirschi S, Ohlmann-Caillard S, Kessler L, Kessler R, Schuller A, Bennedif K, Vargas S, Bonnette P, Chapelier A, Puyo P, Sage E, Bresson J, Caille V, Cerf C, Devaquet J, Dumans-Nizard V, Felten ML, Fischler M, Larbi AG, Leguen M, Ley L, Liu N, Trebbia G, De Miranda S, Douvry B, Gonin F, Grenet D, Hamid AM, Neveu H, Parquin F, Picard C, Roux A, Stern M, Bouillioud F, Cahen P, Colombat M, Dautricourt C, Delahousse M, D'Urso B, Gravisse J, Guth A, Hillaire S, Honderlick P, Lequintrec M, Longchampt E, Mellot F, Scherrer A, Temagoult L, Tricot L, Vasse M, Veyrie C, Zemoura L, Berjaud J, Brouchet L, Dahan M, Le Balle F, Mathe O, Benahoua H, Didier A, Goin AL, Murris M, Crognier L, Fourcade O.

Author information

1
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.
2
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.
3
CHU de Marseille, Aix Marseille Université, Marseille, France.
4
Centre Chirurgical Marie Lannelongue, Service de Chirurgie Thoracique, Vasculaire et Transplantation Cardiopulmonaire, Le Plessis Robinson, France.
5
Hôpital Foch, Suresnes, France.
6
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.
7
Université de Lyon, Lyon, France; Université de Lyon 1, Lyon, France; INRA, UMR_S 754, Lyon, France; Hospices Civils de Lyon, Lyon, France.
8
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.
9
CHU de Bordeaux, Bordeaux, France.
10
CHU de Strasbourg, Strasbourg, France.
11
CHU de Toulouse, Toulouse, France.
12
Hôpital Bichat, Service de Pneumologie B et Transplantation Pulmonaire, Paris, France.
13
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.

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.

PMID:
25329529
PMCID:
PMC4203719
DOI:
10.1371/journal.pone.0109291
[Indexed for MEDLINE]
Free PMC Article

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