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

Publication date: February 2017
Source:Journal of Allergy and Clinical Immunology, Volume 139, Issue 2
Author(s): Josep M. Anto, Jean Bousquet, Mubeccel Akdis, Charles Auffray, Thomas Keil, Isabelle Momas, Dirkje S. Postma, Rudolf Valenta, Magnus Wickman, Anne Cambon-Thomsen, Tari Haahtela, Bart N. Lambrecht, Karin C. Lodrup Carlsen, Gerard H. Koppelman, Jordi Sunyer, Torsten Zuberbier, Isabelle Annesi-Maesano, Albert Arno, Carsten Bindslev-Jensen, Giuseppe De Carlo, Francesco Forastiere, Joachim Heinrich, Marek L. Kowalski, Dieter Maier, Erik Melén, Henriette A. Smit, Marie Standl, John Wright, Anna Asarnoj, Marta Benet, Natalia Ballardini, Judith Garcia-Aymerich, Ulrike Gehring, Stefano Guerra, Cynthia Hohmann, Inger Kull, Christian Lupinek, Mariona Pinart, Ingebjorg Skrindo, Marit Westman, Delphine Smagghe, Cezmi Akdis, Niklas Andersson, Claus Bachert, Stephane Ballereau, Ferran Ballester, Xavier Basagana, Anna Bedbrook, Anna Bergstrom, Andrea von Berg, Bert Brunekreef, Emilie Burte, Kai-Hakon Carlsen, Leda Chatzi, Jonathan M. Coquet, Mirela Curin, Pascal Demoly, Esben Eller, Maria Pia Fantini, Leena von Hertzen, Vergard Hovland, Benedicte Jacquemin, Jocelyne Just, Theresa Keller, Renata Kiss, Manolis Kogevinas, Sibylle Koletzko, Susanne Lau, Irina Lehmann, Nicolas Lemonnier, Mika Mäkelä, Jordi Mestres, Peter Mowinckel, Rachel Nadif, Martijn C. Nawijn, Johan Pellet, Isabelle Pin, Daniela Porta, Fanny Rancière, Emmanuelle Rial-Sebbag, Yvan Saeys, Martijn J. Schuijs, Valerie Siroux, Christina G. Tischer, Mathies Torrent, Raphaelle Varraso, Kalus Wenzel, Cheng-Jian Xu
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.



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