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

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...

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Veröffentlicht in:	Journal of allergy and clinical immunology 2017-02, Vol.139 (2), p.388-399
Hauptverfasser:	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:	Artikel
Sprache:	eng
Schlagworte:	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
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Zusammenfassung:	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.
ISSN:	0091-6749 1097-6825 1097-6825
DOI:	10.1016/j.jaci.2016.12.940