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Review
. 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

Josep M Anto  1 , Jean Bousquet  2 , Mubeccel Akdis  3 , Charles Auffray  4 , Thomas Keil  5 , Isabelle Momas  6 , Dirkje S Postma  7 , Rudolf Valenta  8 , Magnus Wickman  9 , Anne Cambon-Thomsen  10 , Tari Haahtela  11 , Bart N Lambrecht  12 , Karin C Lodrup Carlsen  13 , Gerard H Koppelman  14 , Jordi Sunyer  15 , Torsten Zuberbier  16 , Isabelle Annesi-Maesano  17 , Albert Arno  18 , Carsten Bindslev-Jensen  19 , Giuseppe De Carlo  20 , Francesco Forastiere  21 , Joachim Heinrich  22 , Marek L Kowalski  23 , Dieter Maier  24 , Erik Melén  9 , Henriette A Smit  25 , Marie Standl  22 , John Wright  26 , Anna Asarnoj  27 , Marta Benet  28 , Natalia Ballardini  29 , Judith Garcia-Aymerich  15 , Ulrike Gehring  30 , Stefano Guerra  28 , Cynthia Hohmann  31 , Inger Kull  32 , Christian Lupinek  8 , Mariona Pinart  28 , Ingebjorg Skrindo  13 , Marit Westman  33 , Delphine Smagghe  34 , Cezmi Akdis  3 , Niklas Andersson  35 , Claus Bachert  36 , Stephane Ballereau  4 , Ferran Ballester  37 , Xavier Basagana  28 , Anna Bedbrook  38 , Anna Bergstrom  35 , Andrea von Berg  39 , Bert Brunekreef  40 , Emilie Burte  41 , Kai-Hakon Carlsen  42 , Leda Chatzi  43 , Jonathan M Coquet  12 , Mirela Curin  8 , Pascal Demoly  44 , Esben Eller  19 , Maria Pia Fantini  45 , Leena von Hertzen  11 , Vergard Hovland  42 , Benedicte Jacquemin  28 , Jocelyne Just  46 , Theresa Keller  31 , Renata Kiss  8 , Manolis Kogevinas  15 , Sibylle Koletzko  47 , Susanne Lau  48 , Irina Lehmann  49 , Nicolas Lemonnier  50 , Mika Mäkelä  11 , Jordi Mestres  51 , Peter Mowinckel  42 , Rachel Nadif  41 , Martijn C Nawijn  14 , Johan Pellet  4 , Isabelle Pin  52 , Daniela Porta  21 , Fanny Rancière  6 , Emmanuelle Rial-Sebbag  10 , Yvan Saeys  12 , Martijn J Schuijs  12 , Valerie Siroux  53 , Christina G Tischer  22 , Mathies Torrent  54 , Raphaelle Varraso  41 , Kalus Wenzel  24 , Cheng-Jian Xu  14
Affiliations
Review

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

Josep M Anto et al. J Allergy Clin Immunol. 2017 Feb.

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.

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