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Allergy. 2015 Sep;70(9):1062-78. doi: 10.1111/all.12637. Epub 2015 Jul 14.

Are allergic multimorbidities and IgE polysensitization associated with the persistence or re-occurrence of foetal type 2 signalling? The MeDALL hypothesis.

Author information

  • 1University Hospital, Montpellier, France.
  • 2MACVIA-LR, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon, European Innovation Partnership on Active and Healthy Ageing Reference Site, Paris, France.
  • 3INSERM, VIMA: Ageing and Chronic Diseases Epidemiological and Public Health Approaches, U1168, Paris, France.
  • 4UVSQ, UMR-S 1168, Université Versailles St-Quentin-en-Yvelines, Versailles, France.
  • 5Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
  • 6Hospital del Mar Research Institute (IMIM), Barcelona, Spain.
  • 7CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
  • 8Department of Experimental and Health Sciences, University of Pompeu Fabra (UPF), Barcelona, Spain.
  • 9Sachs' Children's Hospital, Stockholm, Sweden.
  • 10Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
  • 11Institute of Social Medicine, Epidemiology and Health Economics, Charité - Universitätsmedizin Berlin, Berlin, Germany.
  • 12Institute for Clinical Epidemiology and Biometry, University of Wuerzburg, Wuerzburg, Germany.
  • 13Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
  • 14Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland.
  • 15Department of Paediatrics, Oslo University Hospital, Oslo, Norway.
  • 16Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • 17Clinical Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institutet and University Hospital, Stockholm, Sweden.
  • 18Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
  • 19ENT Department, Ghent University Hospital, Gent, Belgium.
  • 20European Institute for Systems Biology and Medicine, Lyon, France.
  • 21EPAR U707 INSERM, Paris, France.
  • 22EPAR UMR-S UPMC, Paris VI, Paris, France.
  • 23Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark.
  • 24UMR Inserm U1027, Université de Toulouse III Paul Sabatier, Toulouse, France.
  • 25University of Oslo, Oslo, Norway.
  • 26Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.
  • 27Department of Epidemiology, Regional Health Service Lazio Region, Rome, Italy.
  • 28Julius Center of Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands.
  • 29Institute of Epidemiology, German Research Centre for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany.
  • 30Department of Pediatric Pulmonology and Pediatric Allergology, GRIAC Research Institute, University Medical Center Groningen, Beatrix Children's Hospital, University of Groningen, Groningen, the Netherlands.
  • 31Department of Immunology, Rheumatology and Allergy, Medical University of Lodz, Lodz, Poland.
  • 32VIB Inflammation Research Center, Ghent University, Ghent, Belgium.
  • 33Biomay AG, Wien, Austria.
  • 34Department of Public Health and Biostatistics, EA 4064, Paris Descartes University, Paris, France.
  • 35Paris Municipal Department of Social Action, Childhood, and Health, Paris, France.
  • 36EFA European Federation of Allergy and Airways Diseases Patients' Associations, Brussels, Belgium.
  • 37Department of Respiratory Medicine, GRIAC Research Institute, University Medical Center Groningen, Beatrix Children's Hospital, University of Groningen, Groningen, the Netherlands.
  • 38Inserm, U823, Grenoble, France.
  • 39Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford, UK.
  • 40Allergy-Centre-Charité at the Department of Dermatology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
  • 41Secretary General of the Global Allergy and Asthma European Network (GA2LEN), Berlin, Germany.
  • 42David Hide Asthma and Allergy Research Centre, Isle of Wight, UK.
  • 43Department of Epidemiology, CAPHRI School of Public Health and Primary Care, Maastricht University, Maastricht, the Netherlands.
  • 44National Heart and Lung Institute, Imperial College London, Royal Brompton Hospital NHS, London, UK.
  • 45Department of Respiratory Diseases, Montpellier University Hospital, Montpellier, France.
  • 46Department of Medicine and Public Health, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
  • 47Allergology Department, Centre de l'Asthme et des Allergies, Hôpital d'Enfants Armand-Trousseau (APHP), Paris, France.
  • 48Institut Pierre Louis d'Epidémiologie et de Santé Publique, Equipe EPAR, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Paris, France.
  • 49Department for Pediatric Pneumology and Immunology, Charité Medical University, Berlin, Germany.
  • 50Département de pédiatrie, CHU de Grenoble, Grenoble Cedex 9, France.
  • 51Area de Salut de Menorca, ib-salut, Illes Balears, Spain.


Allergic diseases [asthma, rhinitis and atopic dermatitis (AD)] are complex. They are associated with allergen-specific IgE and nonallergic mechanisms that may coexist in the same patient. In addition, these diseases tend to cluster and patients present concomitant or consecutive diseases (multimorbidity). IgE sensitization should be considered as a quantitative trait. Important clinical and immunological differences exist between mono- and polysensitized subjects. Multimorbidities of allergic diseases share common causal mechanisms that are only partly IgE-mediated. Persistence of allergic diseases over time is associated with multimorbidity and/or IgE polysensitization. The importance of the family history of allergy may decrease with age. This review puts forward the hypothesis that allergic multimorbidities and IgE polysensitization are associated and related to the persistence or re-occurrence of foetal type 2 signalling. Asthma, rhinitis and AD are manifestations of a common systemic immune imbalance (mesodermal origin) with specific patterns of remodelling (ectodermal or endodermal origin). This study proposes a new classification of IgE-mediated allergic diseases that allows the definition of novel phenotypes to (i) better understand genetic and epigenetic mechanisms, (ii) better stratify allergic preschool children for prognosis and (iii) propose novel strategies of treatment and prevention.

© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


IgE; asthma; atopic dermatitis; polysensitization; rhinitis

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