PMID- 25329529 OWN - NLM STAT- MEDLINE DCOM- 20150702 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 10 DP - 2014 TI - Systematic analysis of blood cell transcriptome in end-stage chronic respiratory diseases. PG - e109291 LID - 10.1371/journal.pone.0109291 [doi] LID - e109291 AB - 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. FAU - Chesne, Julie AU - Chesne J AD - UMR_S 1087 CNRS UMR_6291, l'Institut du Thorax, Universite de Nantes, CHU de Nantes, Centre National de Reference Mucoviscidose Nantes-Roscoff, Nantes, France; Universite de Nantes, Nantes, France. FAU - Danger, Richard AU - Danger R AD - Universite de Nantes, Nantes, France; Institut National de la Sante et de la Recherche Medicale INSERM U1064, and Institut de Transplantation Urologie Nephrologie du Centre Hospitalier Universitaire Hotel Dieu, Nantes, France. FAU - Botturi, Karine AU - Botturi K AD - UMR_S 1087 CNRS UMR_6291, l'Institut du Thorax, Universite de Nantes, CHU de Nantes, Centre National de Reference Mucoviscidose Nantes-Roscoff, Nantes, France; Universite de Nantes, Nantes, France. FAU - Reynaud-Gaubert, Martine AU - Reynaud-Gaubert M AD - CHU de Marseille, Aix Marseille Universite, Marseille, France. FAU - Mussot, Sacha AU - Mussot S AD - Centre Chirurgical Marie Lannelongue, Service de Chirurgie Thoracique, Vasculaire et Transplantation Cardiopulmonaire, Le Plessis Robinson, France. FAU - Stern, Marc AU - Stern M AD - Hopital Foch, Suresnes, France. FAU - Danner-Boucher, Isabelle AU - Danner-Boucher I AD - UMR_S 1087 CNRS UMR_6291, l'Institut du Thorax, Universite de Nantes, CHU de Nantes, Centre National de Reference Mucoviscidose Nantes-Roscoff, Nantes, France. FAU - Mornex, Jean-Francois AU - Mornex JF AD - Universite de Lyon, Lyon, France; Universite de Lyon 1, Lyon, France; INRA, UMR_S 754, Lyon, France; Hospices Civils de Lyon, Lyon, France. FAU - Pison, Christophe AU - Pison C AD - Clinique Universitaire Pneumologie, CHU de Grenoble, Grenoble, France; Universite Joseph Fourier, Grenoble, France; Inserm U1055, Grenoble, France; European Institute of Systems Biology and Medicine, Lyon, France. FAU - Dromer, Claire AU - Dromer C AD - CHU de Bordeaux, Bordeaux, France. FAU - Kessler, Romain AU - Kessler R AD - CHU de Strasbourg, Strasbourg, France. FAU - Dahan, Marcel AU - Dahan M AD - CHU de Toulouse, Toulouse, France. FAU - Brugiere, Olivier AU - Brugiere O AD - Hopital Bichat, Service de Pneumologie B et Transplantation Pulmonaire, Paris, France. FAU - Le Pavec, Jerome AU - Le Pavec J AD - Centre Chirurgical Marie Lannelongue, Service de Chirurgie Thoracique, Vasculaire et Transplantation Cardiopulmonaire, Le Plessis Robinson, France. FAU - Perros, Frederic AU - Perros F AD - Universite Paris-Sud, Le Kremlin-Bicetre, France; AP-HP, Service de Pneumologie, DHU Thorax Innovation, Hopital Bicetre, Le Kremlin-Bicetre, France; INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France. FAU - Humbert, Marc AU - Humbert M AD - Universite Paris-Sud, Le Kremlin-Bicetre, France; AP-HP, Service de Pneumologie, DHU Thorax Innovation, Hopital Bicetre, Le Kremlin-Bicetre, France; INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France. FAU - Gomez, Carine AU - Gomez C AD - CHU de Marseille, Aix Marseille Universite, Marseille, France. FAU - Brouard, Sophie AU - Brouard S AD - Universite de Nantes, Nantes, France; Institut National de la Sante et de la Recherche Medicale INSERM U1064, and Institut de Transplantation Urologie Nephrologie du Centre Hospitalier Universitaire Hotel Dieu, Nantes, France. FAU - Magnan, Antoine AU - Magnan A AD - UMR_S 1087 CNRS UMR_6291, l'Institut du Thorax, Universite de Nantes, CHU de Nantes, Centre National de Reference Mucoviscidose Nantes-Roscoff, Nantes, France; Universite de Nantes, Nantes, France. CN - COLT Consortium LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141020 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (RNA, Messenger) RN - 0 (Receptors, Interleukin-1) RN - 0 (T Cell Transcription Factor 1) RN - 0 (TCF7 protein, human) SB - IM MH - Adult MH - Blood Cells/*metabolism/pathology MH - Case-Control Studies MH - Cell Hypoxia MH - Cluster Analysis MH - Cystic Fibrosis/blood/genetics/pathology MH - *Gene Expression Profiling MH - Gene Ontology MH - Humans MH - Hypertension, Pulmonary/blood/genetics/pathology MH - Lung Diseases/*blood/*genetics/pathology MH - Middle Aged MH - Oligonucleotide Array Sequence Analysis MH - Pulmonary Disease, Chronic Obstructive/blood/genetics/pathology MH - RNA, Messenger/genetics/metabolism MH - Receptors, Interleukin-1/genetics MH - T Cell Transcription Factor 1/genetics PMC - PMC4203719 COIS- Competing Interests: The authors have declared that no competing interests exist. FIR - Antoine, Magnan IR - Antoine M FIR - Jougon, J IR - Jougon J FIR - Velly, J-F IR - Velly JF FIR - Roze, H IR - Roze H FIR - Blanchard, E IR - Blanchard E FIR - Dromer, C IR - Dromer C FIR - Antoine, M IR - Antoine M FIR - Cappello, M IR - Cappello M FIR - Souilamas, R IR - Souilamas R FIR - Ruiz, M IR - Ruiz M FIR - Sokolow, Y IR - Sokolow Y FIR - Vanden Eynden, F IR - Vanden Eynden F FIR - Van Nooten, G IR - Van Nooten G FIR - Barvais, L IR - Barvais L FIR - Berre, J IR - Berre J FIR - Brimioulle, S IR - Brimioulle S FIR - De Backer, D IR - De Backer D FIR - Creteur, J IR - Creteur J FIR - Engelman, E IR - Engelman E FIR - Huybrechts, I IR - Huybrechts I FIR - Ickx, B IR - Ickx B FIR - Preiser, T J C IR - Preiser T FIR - Tuna, T IR - Tuna T FIR - Van Obberghe, L IR - Van Obberghe L FIR - Vancutsem, N IR - Vancutsem N FIR - Vincent, J-L IR - Vincent JL FIR - De Vuyst, P IR - De Vuyst P FIR - Etienne, I IR - Etienne I FIR - Fery, F IR - Fery F FIR - Jacobs, F IR - Jacobs F FIR - Knoop, C IR - Knoop C FIR - Vachiery, J L IR - Vachiery JL FIR - Van den Borne, P IR - Van den Borne P FIR - Wellemans, I IR - Wellemans I FIR - Amand, G IR - Amand G FIR - Collignon, L IR - Collignon L FIR - Giroux, M IR - Giroux M FIR - Arnaud-Crozat, E IR - Arnaud-Crozat E FIR - Bach, V IR - Bach V FIR - Brichon, P-Y IR - Brichon PY FIR - Chaffanjon, P IR - Chaffanjon P FIR - Chavanon, O IR - Chavanon O FIR - de Lambert, A IR - de Lambert A FIR - Fleury, J-P IR - Fleury JP FIR - Guigard, S IR - Guigard S FIR - Hireche, K IR - Hireche K FIR - Pirvu, A IR - Pirvu A FIR - Porcu, P IR - Porcu P FIR - Hacini, R IR - Hacini R FIR - Albaladejo, P IR - Albaladejo P FIR - Allegre, C IR - Allegre C FIR - Anglade, D IR - Anglade D FIR - Bedague, D IR - Bedague D FIR - Bouzat, P IR - Bouzat P FIR - Briot, E IR - Briot E FIR - Carle, O IR - Carle O FIR - Casez-Brasseur, M IR - Casez-Brasseur M FIR - Colas, D IR - Colas D FIR - Dessertaine, G IR - Dessertaine G FIR - Durand, M IR - Durand M FIR - Duret, J IR - Duret J FIR - Fevre, M C IR - Fevre MC FIR - Francony, G IR - Francony G FIR - Gay, S IR - Gay S FIR - Marino, M R IR - Marino MR FIR - Oummahan, B IR - Oummahan B FIR - Protar, D IR - Protar D FIR - Rehm, D IR - Rehm D FIR - Robin, S IR - Robin S FIR - Rossi-Blancher, M IR - Rossi-Blancher M FIR - Saunier, L IR - Saunier L FIR - Bedouch, P IR - Bedouch P FIR - Boignard, A IR - Boignard A FIR - Bouvaist, H IR - Bouvaist H FIR - Briault, A IR - Briault A FIR - Camara, B IR - Camara B FIR - Chanoine, S IR - Chanoine S FIR - Dubuc, M IR - Dubuc M FIR - Lantuejoul, S IR - Lantuejoul S FIR - Quetant, S IR - Quetant S FIR - Maurizi, J IR - Maurizi J FIR - Pavese, P IR - Pavese P FIR - Pison, C IR - Pison C FIR - Saint-Raymond, C IR - Saint-Raymond C FIR - Wion, N IR - Wion N FIR - Cherion, C IR - Cherion C FIR - Grima, R IR - Grima R FIR - Jegaden, O IR - Jegaden O FIR - Maury, J-M IR - Maury JM FIR - Tronc, F IR - Tronc F FIR - Flamens, C IR - Flamens C FIR - Paulus, S IR - Paulus S FIR - Mornex, J-F IR - Mornex JF FIR - Philit, F IR - Philit F FIR - Senechal, A IR - Senechal A FIR - Glerant, J-C IR - Glerant JC FIR - Turquier, S IR - Turquier S FIR - Gamondes, D IR - Gamondes D FIR - Chalabresse, L IR - Chalabresse L FIR - Thivolet-Bejui, F IR - Thivolet-Bejui F FIR - Barnel, C IR - Barnel C FIR - Dubois, C IR - Dubois C FIR - Tiberghien, A IR - Tiberghien A FIR - Le Pimpec-Barthes, F IR - Le Pimpec-Barthes F FIR - Bel, A IR - Bel A FIR - Mordant, P IR - Mordant P FIR - Achouh, P IR - Achouh P FIR - Boussaud, V IR - Boussaud V FIR - Guillemain, R IR - Guillemain R FIR - Meleard, D IR - Meleard D FIR - Bricourt, M O IR - Bricourt MO FIR - Cholley, B IR - Cholley B FIR - Pezella, V IR - Pezella V FIR - Adda, M IR - Adda M FIR - Badier, M IR - Badier M FIR - Bregeon, F IR - Bregeon F FIR - Coltey, B IR - Coltey B FIR - D'Journo, X B IR - D'Journo XB FIR - Dizier, S IR - Dizier S FIR - Doddoli, C IR - Doddoli C FIR - Dufeu, N IR - Dufeu N FIR - Dutau, H IR - Dutau H FIR - Forel, J M IR - Forel JM FIR - Gaubert, J Y IR - Gaubert JY FIR - Gomez, C IR - Gomez C FIR - Leone, M IR - Leone M FIR - Nieves, A IR - Nieves A FIR - Orsini, B IR - Orsini B FIR - Papazian, L IR - Papazian L FIR - Picard, L C IR - Picard LC FIR - Reynaud-Gaubert, M IR - Reynaud-Gaubert M FIR - Roch, A IR - Roch A FIR - Rolain, J M IR - Rolain JM FIR - Sampol, E IR - Sampol E FIR - Secq, V IR - Secq V FIR - Thomas, P IR - Thomas P FIR - Trousse, D IR - Trousse D FIR - Yahyaoui, M IR - Yahyaoui M FIR - Baron, O IR - Baron O FIR - Lacoste, P IR - Lacoste P FIR - Perigaud, C IR - Perigaud C FIR - Roussel, J C IR - Roussel JC FIR - Danner, I IR - Danner I FIR - Haloun, A IR - Haloun A FIR - Magnan, A IR - Magnan A FIR - Tissot, A IR - Tissot A FIR - Lepoivre, T IR - Lepoivre T FIR - Treilhaud, M IR - Treilhaud M FIR - Botturi-Cavailles, K IR - Botturi-Cavailles K FIR - Brouard, S IR - Brouard S FIR - Danger, R IR - Danger R FIR - Loy, J IR - Loy J FIR - Morisset, M IR - Morisset M FIR - Pain, M IR - Pain M FIR - Pares, S IR - Pares S FIR - Reboulleau, D IR - Reboulleau D FIR - Royer, P-J IR - Royer PJ FIR - Dartevelle, P IR - Dartevelle P FIR - Fadel, E IR - Fadel E FIR - Mussot, S IR - Mussot S FIR - Fabre, D IR - Fabre D FIR - Mercier, O IR - Mercier O FIR - Viard, P IR - Viard P FIR - Francois, S IR - Francois S FIR - Cerrina, J IR - Cerrina J FIR - Herve, P IR - Herve P FIR - Le Pavec, J IR - Le Pavec J FIR - Ladurie, F Le Roy IR - Ladurie F FIR - Lamran, L IR - Lamran L FIR - Castier, Y IR - Castier Y FIR - Cerceau, P IR - Cerceau P FIR - Francis, F IR - Francis F FIR - Leseche, G IR - Leseche G FIR - Allou, N IR - Allou N FIR - Augustin, P IR - Augustin P FIR - Boudinet, S IR - Boudinet S FIR - Desmard, M IR - Desmard M FIR - Dufour, G IR - Dufour G FIR - Montravers, P IR - Montravers P FIR - Brugiere, O IR - Brugiere O FIR - Dauriat, G IR - Dauriat G FIR - Jebrak, G IR - Jebrak G FIR - Mal, H IR - Mal H FIR - Marceau, A IR - Marceau A FIR - Metivier, A-C IR - Metivier AC FIR - Thabut, G IR - Thabut G FIR - Ilalne, B Ait IR - Ilalne B FIR - Falcoz, P IR - Falcoz P FIR - Massard, G IR - Massard G FIR - Santelmo, N IR - Santelmo N FIR - Ajob, G IR - Ajob G FIR - Collange, O IR - Collange O FIR - Helms, O IR - Helms O FIR - Hentz, J IR - Hentz J FIR - Roche, A IR - Roche A FIR - Bakouboula, B IR - Bakouboula B FIR - Degot, T IR - Degot T FIR - Dory, A IR - Dory A FIR - Hirschi, S IR - Hirschi S FIR - Ohlmann-Caillard, S IR - Ohlmann-Caillard S FIR - Kessler, L IR - Kessler L FIR - Kessler, R IR - Kessler R FIR - Schuller, A IR - Schuller A FIR - Bennedif, K IR - Bennedif K FIR - Vargas, S IR - Vargas S FIR - Bonnette, P IR - Bonnette P FIR - Chapelier, A IR - Chapelier A FIR - Puyo, P IR - Puyo P FIR - Sage, E IR - Sage E FIR - Bresson, J IR - Bresson J FIR - Caille, V IR - Caille V FIR - Cerf, C IR - Cerf C FIR - Devaquet, J IR - Devaquet J FIR - Dumans-Nizard, V IR - Dumans-Nizard V FIR - Felten, M L IR - Felten ML FIR - Fischler, M IR - Fischler M FIR - Larbi, A G Si IR - Larbi AG FIR - Leguen, M IR - Leguen M FIR - Ley, L IR - Ley L FIR - Liu, N IR - Liu N FIR - Trebbia, G IR - Trebbia G FIR - De Miranda, S IR - De Miranda S FIR - Douvry, B IR - Douvry B FIR - Gonin, F IR - Gonin F FIR - Grenet, D IR - Grenet D FIR - Hamid, A M IR - Hamid AM FIR - Neveu, H IR - Neveu H FIR - Parquin, F IR - Parquin F FIR - Picard, C IR - Picard C FIR - Roux, A IR - Roux A FIR - Stern, M IR - Stern M FIR - Bouillioud, F IR - Bouillioud F FIR - Cahen, P IR - Cahen P FIR - Colombat, M IR - Colombat M FIR - Dautricourt, C IR - Dautricourt C FIR - Delahousse, M IR - Delahousse M FIR - D'Urso, B IR - D'Urso B FIR - Gravisse, J IR - Gravisse J FIR - Guth, A IR - Guth A FIR - Hillaire, S IR - Hillaire S FIR - Honderlick, P IR - Honderlick P FIR - Lequintrec, M IR - Lequintrec M FIR - Longchampt, E IR - Longchampt E FIR - Mellot, F IR - Mellot F FIR - Scherrer, A IR - Scherrer A FIR - Temagoult, L IR - Temagoult L FIR - Tricot, L IR - Tricot L FIR - Vasse, M IR - Vasse M FIR - Veyrie, C IR - Veyrie C FIR - Zemoura, L IR - Zemoura L FIR - Berjaud, J IR - Berjaud J FIR - Brouchet, L IR - Brouchet L FIR - Dahan, M IR - Dahan M FIR - Le Balle, F IR - Le Balle F FIR - Mathe, O IR - Mathe O FIR - Benahoua, H IR - Benahoua H FIR - Didier, A IR - Didier A FIR - Goin, A L IR - Goin AL FIR - Murris, M IR - Murris M FIR - Crognier, L IR - Crognier L FIR - Fourcade, O IR - Fourcade O EDAT- 2014/10/21 06:00 MHDA- 2015/07/03 06:00 PMCR- 2014/10/20 CRDT- 2014/10/21 06:00 PHST- 2014/05/09 00:00 [received] PHST- 2014/08/30 00:00 [accepted] PHST- 2014/10/21 06:00 [entrez] PHST- 2014/10/21 06:00 [pubmed] PHST- 2015/07/03 06:00 [medline] PHST- 2014/10/20 00:00 [pmc-release] AID - PONE-D-14-20804 [pii] AID - 10.1371/journal.pone.0109291 [doi] PST - epublish SO - PLoS One. 2014 Oct 20;9(10):e109291. doi: 10.1371/journal.pone.0109291. eCollection 2014.