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

• Published in: Journal of allergy and clinical immunology Vol. 139; no. 2; pp. 388 - 399
• Main Authors: Anto, Josep M., PhD, Bousquet, Jean, MD, Akdis, Mubeccel, MD, Auffray, Charles, MD, Keil, Thomas, MD, Momas, Isabelle, PhD, Postma, Dirkje S., MD, Valenta, Rudolf, MD, Wickman, Magnus, MD, Cambon-Thomsen, Anne, MD, Haahtela, Tari, MD, Lambrecht, Bart N., MD, Lodrup Carlsen, Karin C., MD, Koppelman, Gerard H., PhD, Sunyer, Jordi, MD, Zuberbier, Torsten, MD, Annesi-Maesano, Isabelle, MD, Arno, Albert, MD, Bindslev-Jensen, Carsten, PhD, De Carlo, Giuseppe, Forastiere, Francesco, MD, Heinrich, Joachim, PhD, Kowalski, Marek L., MD, Maier, Dieter, PhD, Melén, Erik, MD, Smit, Henriette A., PhD, Standl, Marie, PhD, Wright, John, FRPC, Asarnoj, Anna, MD, Benet, Marta, MSc, Ballardini, Natalia, MD, Garcia-Aymerich, Judith, MD, Gehring, Ulrike, PhD, Guerra, Stefano, MD, Hohmann, Cynthia, Dipl Psych, Kull, Inger, PhD, Lupinek, Christian, MD, Pinart, Mariona, PhD, Skrindo, Ingebjorg, MD, Westman, Marit, MD, Smagghe, Delphine, MSc, Akdis, Cezmi, MD, Andersson, Niklas, MSc, Bachert, Claus, MD, Ballereau, Stephane, PhD, Ballester, Ferran, MD, Basagana, Xavier, PhD, Bedbrook, Anna, MSc, Bergstrom, Anna, PhD, von Berg, Andrea, MD, Brunekreef, Bert, PhD, Burte, Emilie, MSc, Carlsen, Kai-Hakon, MD, Chatzi, Leda, MD, Coquet, Jonathan M., PhD, Curin, Mirela, PhD, Demoly, Pascal, MD, Eller, Esben, MD, Fantini, Maria Pia, MD, von Hertzen, Leena, PhD, Hovland, Vergard, MD, Jacquemin, Benedicte, MD, Just, Jocelyne, MD, Keller, Theresa, MSc, Kiss, Renata, MSc, Kogevinas, Manolis, MD, Koletzko, Sibylle, MD, Lau, Susanne, MD, Lehmann, Irina, PhD, Lemonnier, Nicolas, PhD, Mäkelä, Mika, MD, Mestres, Jordi, PhD, Mowinckel, Peter, MSc, Nadif, Rachel, PhD, Nawijn, Martijn C., PhD, Pellet, Johan, MSc, Pin, Isabelle, MD, Porta, Daniela, MD, Rancière, Fanny, PhD, Rial-Sebbag, Emmanuelle, PhD, Saeys, Yvan, PhD, Schuijs, Martijn J., MSc, Siroux, Valerie, PhD, Tischer, Christina G., PhD, Torrent, Mathies, MD, Varraso, Raphaelle, PhD, Wenzel, Kalus, MD, Xu, Cheng-Jian, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Limited 01.02.2017; Elsevier
• Subjects: Adolescent; Air pollution; Allergens - immunology; Allergology; Allergy and Immunology; Animals; Asthma; Child; Chronic illnesses; Cohort Studies; Comorbidity; Europe - epidemiology; Female; Gene Expression Profiling; Genome-Wide Association Study; Humans; Hypersensitivity - epidemiology; Hypersensitivity - genetics; Hypersensitivity - immunology; Hypotheses; Immunization; Immunoglobulin E - metabolism; Immunology; Life Sciences; Medicin och hälsovetenskap; Medicine; Nitrogen dioxide; Phenotype; Socioeconomic factors; Statistical analysis; Studies; Translational Medical Research; Variables; Young Adult; BAMSE; GWAS; atopic dermatitis; Danish Allergy Research Centre; National Institutes of Health; Environment and Childhood Asthma; Mechanisms of the Development of ALLergy; Pollution and Asthma Risk: an Infant Study; ENRIECO; Prevention and Incidence of Asthma and Mite Allergy; EGEA; EDEN; Environmental Health Risks in European Birth Cohorts; allergy; GA 2LEN; Infancia y Medio Ambiente; Asthma; EU; Chitinase-3–like protein 1; German Infant Study on the Influence of Nutrition Intervention PLUS Environmental and Genetic Influences on Allergy Development; IL-1RL1; CHI3L1; MAS; Personalized, predictive, preventative, and participatory; IL-1 receptor–like 1; Rome and Bologna Birth Cohorts; German Multicenter Allergy Study; Life-Style Factors on the Development of the Immune System and Allergies in East and West Germany PLUS the Influence of Traffic Emissions and Genetics; rhinitis; Barn/Children Allergy/Asthma Milieu Stockholm Epidemiologic; LISAplus; Epidemiological study on the Genetics and Environment of Asthma, Bronchial Hyperresponsiveness and Atopy; Genome-wide association study; Etude des Déterminants pré et post natals du développement et de la santé de l' Enfant; GINIplus; INMA; MeDALL; ECA; P4; Mother-Child Cohort in Crete; NIH; PARIS; CQ; DARC; ROBBIC; RHEA; European Union; PIAMA; Core Questionnaire; Global Allergy and Asthma European Network
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2016.12.940

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.