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6 results on '"Auffray, Charle"'

1. Large-Scale Label-Free Quantitative Mapping of the Sputum Proteome

Author

Burg, Dominic, Schofield, James P R, Brandsma, Joost, Staykova, Doroteya, Folisi, Caterina, Bansal, Aruna, Nicholas, Ben, Xian, Yang, Rowe, Anthony, Corfield, Julie, Wilson, Susan, Ward, Jonathan, Lutter, Rene, Fleming, Louise, Shaw, Dominick E, Bakke, Per S, Caruso, Massimo, Dahlen, Sven-Erik, Fowler, Stephen J, Hashimoto, Simone, Horváth, Ildikó, Howarth, Peter, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandström, Thoma, Singer, Florian, Sun, Kai, Pandis, Ioanni, Auffray, Charle, Sousa, Ana R, Adcock, Ian M, Chung, Kian Fan, Sterk, Peter J, Djukanović, Ratko, Skipp, Paul J, The U-Biopred Study Group, Null, Montuschi, Paolo (ORCID:0000-0001-5589-1750), Burg, Dominic, Schofield, James P R, Brandsma, Joost, Staykova, Doroteya, Folisi, Caterina, Bansal, Aruna, Nicholas, Ben, Xian, Yang, Rowe, Anthony, Corfield, Julie, Wilson, Susan, Ward, Jonathan, Lutter, Rene, Fleming, Louise, Shaw, Dominick E, Bakke, Per S, Caruso, Massimo, Dahlen, Sven-Erik, Fowler, Stephen J, Hashimoto, Simone, Horváth, Ildikó, Howarth, Peter, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandström, Thoma, Singer, Florian, Sun, Kai, Pandis, Ioanni, Auffray, Charle, Sousa, Ana R, Adcock, Ian M, Chung, Kian Fan, Sterk, Peter J, Djukanović, Ratko, Skipp, Paul J, The U-Biopred Study Group, Null, and Montuschi, Paolo (ORCID:0000-0001-5589-1750)

Abstract

Analysis of induced sputum supematant is a minimally invasive approach to study the epithelial lining fluid and, thereby, provide insight into normal lung biology and the pathobiology of lung diseases. We present here a novel proteomics approach to sputum analysis developed within the U-BIOPRED (unbiased biomarkers predictive of respiratory disease outcomes) international project. We present practical and analytical techniques to optimize the detection of robust biomarkers in proteomic studies. The normal sputum proteome was derived using data-independent HDMSE applied to 40 healthy nonsmoking participants, which provides an essential baseline from which to compare modulation of protein expression in respiratory diseases. The "core" sputum proteome (proteins detected in >= 40% of participants) was composed of 284 proteins, and the extended proteome (proteins detected in >= 3 participants) contained 1666 proteins. Quality control procedures were developed to optimize the accuracy and consistency of measurement of sputum proteins and analyze the distribution of sputum proteins in the healthy population. The analysis showed that quantitation of proteins by HDMSE is influenced by several factors, with some proteins being measured in all participants' samples and with low measurement variance between samples from the same patient. The measurement of some proteins is highly variable between repeat analyses, susceptible to sample processing effects, or difficult to accurately quantify by mass spectrometry. Other proteins show high interindividual variance. We also highlight that the sputum proteome of healthy individuals is related to sputum neutrophil levels, but not gender or allergic sensitization. We illustrate the importance of design and interpretation of disease biomarker studies considering such protein population and technical measurement variance.

Published
2018

2. Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis

Author

Takahashi, Kentaro, Pavlidis, Stelio, Ng Kee Kwong, Francoi, Hoda, Uruj, Rossios, Christo, Sun, Kai, Loza, Matthew, Baribaud, Fred, Chanez, Pascal, Fowler, Steve J, Horvath, Ildiko, Montuschi, Paolo, Singer, Florian, Musial, Jacek, Dahlen, Barbro, Dahlen, Sven-Eric, Krug, Norbert, Sandstrom, Thoma, Shaw, Dominic E, Lutter, Rene, Bakke, Per, Fleming, Louise J, Howarth, Peter H, Caruso, Massimo, Sousa, Ana R, Corfield, Julie, Auffray, Charle, De Meulder, Bertrand, Lefaudeux, Diane, Djukanovic, Ratko, Sterk, Peter J, Guo, Yike, Adcock, Ian M, Chung, Kian Fan, Montuschi, Paolo (ORCID:0000-0001-5589-1750), Takahashi, Kentaro, Pavlidis, Stelio, Ng Kee Kwong, Francoi, Hoda, Uruj, Rossios, Christo, Sun, Kai, Loza, Matthew, Baribaud, Fred, Chanez, Pascal, Fowler, Steve J, Horvath, Ildiko, Montuschi, Paolo, Singer, Florian, Musial, Jacek, Dahlen, Barbro, Dahlen, Sven-Eric, Krug, Norbert, Sandstrom, Thoma, Shaw, Dominic E, Lutter, Rene, Bakke, Per, Fleming, Louise J, Howarth, Peter H, Caruso, Massimo, Sousa, Ana R, Corfield, Julie, Auffray, Charle, De Meulder, Bertrand, Lefaudeux, Diane, Djukanovic, Ratko, Sterk, Peter J, Guo, Yike, Adcock, Ian M, Chung, Kian Fan, and Montuschi, Paolo (ORCID:0000-0001-5589-1750)

Abstract

Severe asthma patients with a significant smoking history have airflow obstruction with reported neutrophilia. We hypothesise that multi-omic analysis will enable the definition of smoking and ex-smoking severe asthma molecular phenotypes.The U-BIOPRED cohort of severe asthma patients, containing current-smokers (CSA), ex-smokers (ESA), nonsmokers and healthy nonsmokers was examined. Blood and sputum cell counts, fractional exhaled nitric oxide and spirometry were obtained. Exploratory proteomic analysis of sputum supernatants and transcriptomic analysis of bronchial brushings, biopsies and sputum cells was performed.Colony-stimulating factor (CSF) 2 protein levels were increased in CSA sputum supernatants, with azurocidin 1, neutrophil elastase and CXCL8 upregulated in ESA. Phagocytosis and innate immune pathways were associated with neutrophilic inflammation in ESA. Gene set variation analysis of bronchial epithelial cell transcriptome from CSA showed enrichment of xenobiotic metabolism, oxidative stress and endoplasmic reticulum stress compared to other groups. CXCL5 and matrix metallopeptidase 12 genes were upregulated in ESA and the epithelial protective genes, mucin 2 and cystatin SN, were downregulated.Despite little difference in clinical characteristics, CSA were distinguishable from ESA subjects at the sputum proteomic level, with CSA patients having increased CSF2 expression and ESA patients showing sustained loss of epithelial barrier processes.

Published
2018

3. Integrative systems medicine approaches to identify molecular targets in lymphoid malignancies

Author

Frazzi, Raffaele, Auffray, Charle, Ferrari, Angela, Filippini, Perla, Rutella, Sergio, Cesario, Alfredo, Cesario, Alfredo (ORCID:0000-0003-4687-0709), Frazzi, Raffaele, Auffray, Charle, Ferrari, Angela, Filippini, Perla, Rutella, Sergio, Cesario, Alfredo, and Cesario, Alfredo (ORCID:0000-0003-4687-0709)

Abstract

Although survival rates for lymphoproliferative disorders are steadily increasing both in the US and in Europe, there is need for optimizing front-line therapies and developing more effective salvage strategies. Recent advances in molecular genetics have highlighted the biological diversity of lymphoproliferative disorders. In particular, integrative approaches including whole genome sequencing, whole exome sequencing, and transcriptome or RNA sequencing have been instrumental to the identification of molecular targets for treatment. Herein, we will discuss how genomic, epigenomic and proteomic approaches in lymphoproliferative disorders have supported the discovery of molecular lesions and their therapeutic targeting in the clinic.

Published
2016

4. P4 medicine needs P4 education

Author

Cesario, Alfredo, Auffray, Charle, Russo, Patrizia, Hood, Leroy, Cesario, Alfredo (ORCID:0000-0003-4687-0709), Cesario, Alfredo, Auffray, Charle, Russo, Patrizia, Hood, Leroy, and Cesario, Alfredo (ORCID:0000-0003-4687-0709)

Abstract

This monographic issue of Current Pharmacological Design discusses extensively on the innovative paradigms for disease control in Active and Healthy Ageing. Wellness, as a status to be achieved and maintained in our lives, getting longer and hopefully healtier, is the new and comprehensive declination of "health" itself, leading the shaping of research and research policy in the health domain worldwide. Many of the contributions describe the state of the art -and beyond- approaches for the most common diseases based on the available medical knowledge; two, in particular (Bousquet J et al., Cesario A, et al.), extend to the innovative approaches defined in the framework of the holistic and integrative philosophy of the Predictive, Preventive, Personalized and Participatory (P4) Systems Medicine. The availability of more and more powerful technologies to extract data coupled with the inclusion of information coming from the nonstrictly-medical sphere of the patient/individual and his/her lifestyle along with the increase in computational power, will definitely set the stage for a paradigm-shift in bio-medicine with deep ethical and societal impact. The brief comment that follows speculates about the implications of this transition from the educational perspective taking stock of the direct experience of the Authors in the consultation process active in the scientific community.

Published
2014

5. DNA methylation in childhood asthma

Author

Mariona Bustamante, Francesco Forastiere, Henriette A. Smit, Petter Mowinckel, Marjan Kerkhof, Tari Haahtela, Martijn C. Nawijn, Raul Aguirre-Gamboa, Dan Mason, Mihai G. Netea, Cisca Wijmenga, Raf Azad, Vegard Hovland, John Wright, Josep M. Antó, Cilla Söderhäll, Pieter van der Vlies, William O.C.M. Cookson, Bianca van Rijkom, Lovisa E. Reinius, Soesma A Jankipersadsing, Leda Chatzi, Nour Baïz, Erik Melén, Daniela Porta, Olena Gruzieva, Juha Kere, Isabella Annesi-Maesano, Maties Torrent, Charles Auffray, Cleo C. van Diemen, Manolis Kogevinas, Davide Gori, Johann Pellet, Jose Ramon Bilbao, Harri Alenius, Göran Pershagen, Sabrina Llop, Miriam F. Moffatt, Nathanaël Lemonnier, Ashok Kumar, Simon Kebede Merid, Nanna Fyhrquist, Stephane Ballereau, Tiina Laatikainen, Cheng-Jian Xu, Johan C. de Jongste, Marc Jan Bonder, Judith Garcia-Aymerich, Karin C. Lødrup Carlsen, J Sunyer, Mikel Basterrechea, Dario Greco, Yang Li, Jean Bousquet, Ulrike Gehring, Catherine Laprise, Maria Pia Fantini, Rosemary R. C. McEachan, Bert Brunekreef, Stefano Guerra, Gerard H. Koppelman, Cornelis J. Vermeulen, Andréanne Morin, Carmen Iñiguez, Kai-Håkon Carlsen, Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, CIBER de Epidemiología y Salud Pública (CIBERESP), IMIM-Hospital del Mar, Generalitat de Catalunya, Universitat Pompeu Fabra [Barcelona] (UPF), Karolinska Institutet [Stockholm], University of Helsinki, King‘s College London, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Stockholm County Council, Aging Research Center [Karolinska Institutet] (ARC ), Stockholm University-Karolinska Institutet [Stockholm], Keck School of Medicine [Los Angeles], University of Southern California (USC), Azienda Sanitaria Locale [ROMA] (ASL), McGill University and Genome Quebec Innovation Centre, Département des Sciences Fondamentales [Chicoutimi] (DSF), Université du Québec à Chicoutimi (UQAC), European Institute for Systems Biology and Medicine (EISBM), Arizona Respiratory Center, Radboud University Medical Center [Nijmegen], Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Department of Dermatology, Allergology and Venereology, Clinicum, Medicum, Department of Bacteriology and Immunology, HUS Inflammation Center, One Health Chemisch, dIRAS RA-2, Pediatrics, RS: NUTRIM - R3 - Respiratory & Age-related Health, Complexe Genetica, RS: NUTRIM - R4 - Gene-environment interaction, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Xu, Cheng-Jian, Söderhäll, Cilla, Bustamante, Mariona, Baïz, Nour, Gruzieva, Olena, Gehring, Ulrike, Mason, Dan, Chatzi, Leda, Basterrechea, Mikel, Llop, Sabrina, Torrent, Matie, Forastiere, Francesco, Fantini, Maria Pia, Carlsen, Karin C Lødrup, Haahtela, Tari, Morin, Andréanne, Kerkhof, Marjan, Merid, Simon Kebede, van Rijkom, Bianca, Jankipersadsing, Soesma A., Bonder, Marc Jan, Ballereau, Stephane, Vermeulen, Cornelis J., Aguirre-Gamboa, Raul, de Jongste, Johan C., Smit, Henriette A., Kumar, Ashish, Pershagen, Göran, Guerra, Stefano, Garcia-Aymerich, Judith, Greco, Dario, Reinius, Lovisa, McEachan, Rosemary R.C., Azad, Raf, Hovland, Vegard, Mowinckel, Petter, Alenius, Harri, Fyhrquist, Nanna, Lemonnier, Nathanaël, Pellet, Johann, Auffray, Charle, van der Vlies, Pieter, van Diemen, Cleo C., Li, Yang, Wijmenga, Cisca, Netea, Mihai G., Moffatt, Miriam F., Cookson, William O.C.M., Anto, Josep M., Bousquet, Jean, Laatikainen, Tiina, Laprise, Catherine, Carlsen, Kai-Håkon, Gori, Davide, Porta, Daniela, Iñiguez, Carmen, Bilbao, Jose Ramon, Kogevinas, Manoli, Wright, John, Brunekreef, Bert, Kere, Juha, Nawijn, Martijn C., Annesi-Maesano, Isabella, Sunyer, Jordi, Melén, Erik, and Koppelman, Gerard H.

Subjects
Male, 0301 basic medicine, Allergy, Cytotoxic, T-Lymphocytes, [SDV]Life Sciences [q-bio], Respiratory System, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], CHILDREN, Immunoglobulin E, Epigenesis, Genetic, Child, POPULATION, education.field_of_study, biology, Methylation, 3. Good health, CpG site, Child, Preschool, DNA methylation, Female, BIOS Consortium, Life Sciences & Biomedicine, Pulmonary and Respiratory Medicine, Population, PHENOTYPES, IMMUNITY, 03 medical and health sciences, Critical Care Medicine, Genetic, General & Internal Medicine, medicine, Humans, COHORT, Epigenetics, IGE, EXPOSURE, Preschool, education, Asthma, Science & Technology, business.industry, RHINITIS, DNA, DNA Methylation, medicine.disease, Eosinophils, 030104 developmental biology, 3121 General medicine, internal medicine and other clinical medicine, Immunology, biology.protein, GENOMEWIDE ASSOCIATION, CpG Islands, business, COLLECTION, T-Lymphocytes, Cytotoxic, Epigenesis, Genome-Wide Association Study
Abstract

Background: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. Methods: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4–5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design. After identification of differentially methylated CpG sites in the discovery analysis, we did a validation study in children (4–16 years; 247 cases and 2949 controls) from six additional European cohorts and meta-analysed the results. We next investigated whether replicated CpG sites in cord blood predict later asthma in 1316 children. We subsequently investigated cell-type-specific methylation of the identified CpG sites in eosinophils and respiratory epithelial cells and their related gene-expression signatures. We studied cell-type specificity of the asthma association of the replicated CpG sites in 455 respiratory epithelial cell samples, collected by nasal brushing of 16-year-old children as well as in DNA isolated from blood eosinophils (16 with asthma, eight controls [age 2–56 years]) and compared this with whole-blood DNA samples of 74 individuals with asthma and 93 controls (age 1–79 years). Whole-blood transcriptional profiles associated with replicated CpG sites were annotated using RNA-seq data of subsets of peripheral blood mononuclear cells sorted by fluorescence-activated cell sorting. Findings: 27 methylated CpG sites were identified in the discovery analysis. 14 of these CpG sites were replicated and passed genome-wide significance (p

Published
2018

6. Mechanisms of the Development of Allergy (MeDALL) : Introducing novel concepts in allergy phenotypes

Author

Isabelle Pin, Stefano Guerra, Cynthia Hohmann, Marit Westman, Mariona Pinart, Jordi Mestres, Martijn C. Nawijn, Tari Haahtela, Dirkje S. Postma, Torsten Zuberbier, Kalus Wenzel, Mika J. Mäkelä, Fanny Rancière, Karin C. Lødrup Carlsen, Mirela Curin, Dieter Maier, Stephane Ballereau, Johan Pellet, Cezmi A. Akdis, Claus Bachert, Erik Melén, Emilie Burte, Bénédicte Jacquemin, Jean Bousquet, Anne Cambon-Thomsen, Christian Lupinek, I. Skrindo, Mübeccel Akdis, Rachel Nadif, Bert Brunekreef, Judith Garcia-Aymerich, Jonathan M. Coquet, Valérie Siroux, Inger Kull, Peter Mowinckel, Bart N. Lambrecht, Renata Kiss, Anna Bedbrook, Ferran Ballester, Kai-Håkon Carlsen, Yvan Saeys, Raphaëlle Varraso, Emmanuelle Rial-Sebbag, Giuseppe De Carlo, Sibylle Koletzko, Maria Pia Fantini, Joachim Heinrich, Jordi Sunyer, Andrea von Berg, Gerard H. Koppelman, Theresa Keller, Vergard Hovland, John Wright, Nicolas Lemonnier, Josep M. Antó, Marta Benet, Rudolf Valenta, Irina Lehmann, Susanne Lau, Francesco Forastiere, Isabelle Momas, Niklas Andersson, Albert Arno, Pascal Demoly, Jocelyne Just, Anna Bergström, Charles Auffray, Henriette A. Smit, Delphine Smagghe, Manolis Kogevinas, Anna Asarnoj, Marie Standl, Daniela Porta, I. Annesi-Maesano, Martijn J. Schuijs, Ulrike Gehring, Mathies Torrent, Thomas Keil, Christina Tischer, Cheng-Jian Xu, Esben Eller, Marek L. Kowalski, Carsten Bindslev-Jensen, Leda Chatzi, Magnus Wickman, Natalia Ballardini, Leena von Hertzen, Xavier Basagaña, Anto, Josep M., Bousquet, Jean, Akdis, Mubeccel, Auffray, Charle, Keil, Thoma, Momas, Isabelle, Postma, Dirkje S., Valenta, Rudolf, Wickman, Magnu, Cambon-Thomsen, Anne, Haahtela, Tari, Lambrecht, Bart N., Lodrup Carlsen, Karin C., Koppelman, Gerard H., Sunyer, Jordi, Zuberbier, Torsten, Annesi-Maesano, Isabelle, Arno, Albert, Bindslev-Jensen, Carsten, De Carlo, Giuseppe, Forastiere, Francesco, Heinrich, Joachim, Kowalski, Marek L., Maier, Dieter, Melén, Erik, Smit, Henriette A., Standl, Marie, Wright, John, Asarnoj, Anna, Benet, Marta, Ballardini, Natalia, Garcia-Aymerich, Judith, Gehring, Ulrike, Guerra, Stefano, Hohmann, Cynthia, Kull, Inger, Lupinek, Christian, Pinart, Mariona, Skrindo, Ingebjorg, Westman, Marit, Smagghe, Delphine, Akdis, Cezmi, Andersson, Nikla, Bachert, Clau, Ballereau, Stephane, Ballester, Ferran, Basagana, Xavier, Bedbrook, Anna, Bergstrom, Anna, von Berg, Andrea, Brunekreef, Bert, Burte, Emilie, Carlsen, Kai-Hakon, Chatzi, Leda, Coquet, Jonathan M., Curin, Mirela, Demoly, Pascal, Eller, Esben, Fantini, Maria Pia, von Hertzen, Leena, Hovland, Vergard, Jacquemin, Benedicte, Just, Jocelyne, Keller, Theresa, Kiss, Renata, Kogevinas, Manoli, Koletzko, Sibylle, Lau, Susanne, Lehmann, Irina, Lemonnier, Nicola, Mäkelä, Mika, Mestres, Jordi, Mowinckel, Peter, Nadif, Rachel, Nawijn, Martijn C., Pellet, Johan, Pin, Isabelle, Porta, Daniela, Rancière, Fanny, Rial-Sebbag, Emmanuelle, Saeys, Yvan, Schuijs, Martijn J., Siroux, Valerie, Tischer, Christina G., Torrent, Mathie, Varraso, Raphaelle, Wenzel, Kalu, Xu, Cheng-Jian, dIRAS RA-2, LS IRAS EEPI ME (Milieu epidemiologie), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), European Institute for Systems Biology and Medicine (EISBM), Epidémiologie Environnementale : Impact Sanitaire des Pollutions (EA 4064), Université Paris Descartes - Paris 5 (UPD5), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Centre de l'Asthme et des Allergies [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut Albert Bonniot, Département de pédiatrie, CHU Grenoble-Hôpital Michallon, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Groningen Research Institute for Asthma and COPD (GRIAC)

Subjects
0301 basic medicine, Allergy, Genome-wide association study, Comorbidity, Immunoglobulin E, medicine.disease_cause, Cohort Studies, Translational Research, Biomedical, 0302 clinical medicine, Allergen, REGULATORY B-CELLS, PRECISION MEDICINE, Medicine, BIRTH COHORT INFANTS, ATOPIC-DERMATITIS, Immunology and Allergy, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Child, media_common, biology, atopic dermatitis, Atopic dermatitis, 3. Good health, Europe, Multicenter Study, CHRONIC RESPIRATORY-DISEASES, rhiniti, Phenotype, INNER-CITY CHILDREN, Biomarker (medicine), Female, atopic dermatiti, Adolescent, EUROPEAN INNOVATION PARTNERSHIP, Immunology, review, 03 medical and health sciences, EARLY-LIFE, Young Adult, rhinitis, Asthma, Atopic Dermatitis, Rhinitis, Hypersensitivity, Journal Article, media_common.cataloged_instance, Animals, Humans, European union, MOUNTAIN CEDAR POLLINOSIS, business.industry, Gene Expression Profiling, CHILDHOOD ASTHMA, Allergens, medicine.disease, allergy, 030104 developmental biology, 030228 respiratory system, biology.protein, Immunization, business, Genome-Wide Association Study
Abstract

Asthma, rhinitis, and eczema are complex diseases with multiple genetic and environmental factors interlinked through IgE-associated and non–IgE-associated mechanisms. Mechanisms of the Development of ALLergy (MeDALL; EU FP7-CP-IP; project no: 261357; 2010-2015) studied the complex links of allergic diseases at the clinical and mechanistic levels by linking epidemiologic, clinical, and mechanistic research, including invivo and invitro models. MeDALL integrated 14 European birth cohorts, including 44,010 participants and 160 cohort follow-ups between pregnancy and age 20years. Thirteen thousand children were prospectively followed after puberty by using a newly standardized MeDALL Core Questionnaire. Amicroarray developed for allergen molecules with increased IgE sensitivity was obtained for 3,292 children. Estimates of air pollution exposure from previous studies were available for 10,000 children. Omics data included those from historical genome-wide association studies (23,000 children) and DNA methylation (2,173), targeted multiplex biomarker (1,427), andtranscriptomic (723) studies. Using classical epidemiology and machine-learning methods in 16,147 children aged 4years and 11,080 children aged 8years, MeDALL showed the multimorbidity of eczema, rhinitis, and asthma and estimated that only 38% of multimorbidity was attributable to IgE sensitization. MeDALL has proposed a new vision of multimorbidity independent of IgE sensitization, and has shown that monosensitization and polysensitization represent 2 distinct phenotypes. The translational component of MeDALL is shown by the identification of a novel allergic phenotype characterized by polysensitization and multimorbidity, which is associated with the frequency, persistence, and severity of allergic symptoms. The results of MeDALL will help integrate personalized, predictive, preventative, and participatory approaches in allergic diseases.

Published
2017

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