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J Allergy Clin Immunol. 2017 Feb;139(2):388-399. doi: 10.1016/j.jaci.2016.12.940.

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

Author information

  • 1ISGLoBAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; IMIM (Hospital del Mar Research Institute), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain. Electronic address: jmanto@isglobal.org.
  • 2University Hospital, Montpellier, France; MACVIA-France, Contre les MAladies Chroniques pour un Vieillissement Actif en France, European Innovation Partnership on Active and Healthy Ageing Reference Site, Montpellier; INSERM, U1168, Ageing and chronic diseases Epidemiological and public health approaches, Villejuif, and UVSQ, UMR-S 1168, Univ Versaille St-Quentin-en-Yvelynes, Montigny le Bretonneux, France. Electronic address: jean.bousquet@orange.fr.
  • 3Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
  • 4European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL, Université de Lyon, Lyon, France.
  • 5Institute of Social Medicine, Epidemiology and Health Economics, Charité-Universitätsmedizin Berlin, Berlin, and the Institute for Clinical Epidemiology and Biometry, University of Wuerzburg, Wuerzburg, Germany.
  • 6Department of Public health and health products, Paris Descartes University-Sorbonne Paris Cité, EA 4064, and Paris Municipal Department of Social Action, Childhood, and Health, Paris, France.
  • 7University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • 8Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
  • 9Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
  • 10UMR Inserm U1027 and Université de Toulouse III Paul Sabatier, Toulouse, France.
  • 11Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland.
  • 12VIB Inflammation Research Center, Ghent University, Ghent, Belgium.
  • 13Department of Paediatrics, Oslo University Hospital, and the Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • 14Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • 15ISGLoBAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; IMIM (Hospital del Mar Research Institute), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
  • 16Allergy-Centre-Charité at the Department of Dermatology, Charité-Universitätsmedizin Berlin, and Secretary General of the Global Allergy and Asthma European Network (GA(2)LEN), Berlin, Germany.
  • 17EPAR U707 INSERM, Paris and EPAR UMR-S UPMC, Paris VI, Paris, France.
  • 18Onmedic Networks, Barcelona, Spain.
  • 19Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark.
  • 20EFA European Federation of Allergy and Airways Diseases Patients' Associations, Brussels, Belgium.
  • 21Department of Epidemiology, Regional Health Service Lazio Region, Rome, Italy.
  • 22Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
  • 23Department of Immunology, Rheumatology and Allergy, Medical University of Lodz, Lodz, Poland.
  • 24Biomax Informatics AG, Munich, Germany.
  • 25Julius Center of Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands.
  • 26Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford, United Kingdom.
  • 27Clinical Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, and Astrid Lindgren Children's Hospital, Department of Pediatric Pulmonology and Allergy, Karolinska University Hospital, Stockholm, Sweden.
  • 28ISGLoBAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
  • 29Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; St John's Institute of Dermatology, King's College London, London, United Kingdom.
  • 30Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
  • 31Institute of Social Medicine, Epidemiology and Health Economics, Charité-Universitätsmedizin, Berlin, Germany.
  • 32Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
  • 33Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, and Department of ENT diseases, Karolinska University Hospital, Stockholm, Sweden.
  • 34Inserm Transfert, Paris, France.
  • 35Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
  • 36ENT Department, Ghent University Hospital, Ghent, Belgium.
  • 37Environment and Health Area, Centre for Public Health Research (CSISP); CIBERESP, Department of Nursing, University of Valencia, Valencia, Spain.
  • 38MACVIA-France, Contre les MAladies Chroniques pour un Vieillissement Actif en France, European Innovation Partnership on Active and Healthy Ageing Reference Site, Montpellier.
  • 39Research Institute, Department of Pediatrics, Marien-Hospital, Wesel, Germany.
  • 40Julius Center of Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands; Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
  • 41INSERM, U1168, Ageing and chronic diseases Epidemiological and public health approaches, Villejuif, and UVSQ, UMR-S 1168, Univ Versaille St-Quentin-en-Yvelynes, Montigny le Bretonneux, France.
  • 42Department of Paediatrics, Oslo University Hospital and University of Oslo, Oslo, Norway.
  • 43Department of Social Medicine, Faculty of Medicine, University of Crete, Crete, Greece.
  • 44Department of Respiratory Diseases, Montpellier University Hospital, Montpellier, France.
  • 45Department of Medicine and Public Health, Alma Mater Studiorum-University of Bologna, Bologna, Italy.
  • 46Allergology Department, Centre de l'Asthme et des Allergies, Hôpital d'Enfants Armand-Trousseau (APHP), and Sorbonne Universités, UPMC Univ Paris Institut Pierre Louis d'Epidémiologie et de Santé Publique, Equipe EPAR, Paris, France.
  • 47Division of Paediatric Gastroenterology and Hepatology, Ludwig-Maximilians-Universität of Munich, Munich, Germany.
  • 48Department for Pediatric Pneumology and Immunology, Charité Medical University, Berlin, Germany.
  • 49Department of Environmental Immunology/Core Facility Studies, Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany.
  • 50Institut Albert Bonniot à Grenoble (Institute for Advanced Biosciences), Grenoble, France.
  • 51Chemotargets SL and Chemogenomics Laboratory, GRIB Unit, IMIM-Hospital del Mar and University Pompeu Fabra, Barcelona, Spain.
  • 52Département de pédiatrie, CHU de Grenoble, Grenoble, France.
  • 53Inserm, U823, Grenoble, France.
  • 54ISGLoBAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; ib-salut, Area de Salut de Menorca, Menorca, Spain.

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 in vivo and in vitro models. MeDALL integrated 14 European birth cohorts, including 44,010 participants and 160 cohort follow-ups between pregnancy and age 20 years. Thirteen thousand children were prospectively followed after puberty by using a newly standardized MeDALL Core Questionnaire. A microarray 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), and transcriptomic (723) studies. Using classical epidemiology and machine-learning methods in 16,147 children aged 4 years and 11,080 children aged 8 years, 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.

KEYWORDS:

Asthma; allergy; atopic dermatitis; rhinitis

PMID:
28183433
DOI:
10.1016/j.jaci.2016.12.940
[PubMed - in process]

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