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RESEARCH PRODUCT

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

Isabelle PinStefano GuerraCynthia HohmannMarit WestmanMariona PinartJordi MestresMartijn C. NawijnTari HaahtelaDirkje S. PostmaTorsten ZuberbierKalus WenzelMika J. MäkeläFanny RancièreKarin C. Lødrup CarlsenMirela CurinDieter MaierStephane BallereauJohan PelletCezmi A. AkdisClaus BachertErik MelénEmilie BurteBénédicte JacqueminJean BousquetJean BousquetAnne Cambon-thomsenChristian LupinekI. SkrindoMübeccel AkdisRachel NadifBert BrunekreefJudith Garcia-aymerichJonathan M. CoquetValérie SirouxInger KullPeter MowinckelBart N. LambrechtRenata KissAnna BedbrookFerran BallesterKai-håkon CarlsenYvan SaeysRaphaëlle VarrasoEmmanuelle Rial-sebbagGiuseppe De CarloSibylle KoletzkoMaria Pia FantiniJoachim HeinrichJordi SunyerAndrea Von BergGerard H. KoppelmanTheresa KellerVergard HovlandJohn WrightNicolas LemonnierJosep M. AntóMarta BenetRudolf ValentaIrina LehmannSusanne LauForastiere FrancescoIsabelle MomasNiklas AnderssonAlbert ArnoPascal DemolyJocelyne JustAnna BergströmCharles AuffrayHenriette A. SmitDelphine SmaggheManolis KogevinasAnna AsarnojMarie StandlDaniela PortaI. Annesi-maesanoMartijn J. SchuijsUlrike GehringMathies TorrentThomas KeilChristina TischerCheng-jian XuEsben EllerMarek L. KowalskiCarsten Bindslev-jensenLeda ChatziMagnus WickmanNatalia BallardiniNatalia BallardiniLeena Von HertzenXavier Basagaña

subject

0301 basic medicineAllergyGenome-wide association studyComorbidityImmunoglobulin Emedicine.disease_causeCohort StudiesTranslational Research Biomedical0302 clinical medicineAllergenREGULATORY B-CELLSPRECISION MEDICINEMedicineBIRTH COHORT INFANTSATOPIC-DERMATITISImmunology and Allergy[SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/AllergologyChildmedia_commonbiologyatopic dermatitisAtopic dermatitis3. Good healthEuropeMulticenter StudyCHRONIC RESPIRATORY-DISEASESrhinitiPhenotypeINNER-CITY CHILDRENBiomarker (medicine)Femaleatopic dermatitiAdolescentEUROPEAN INNOVATION PARTNERSHIPImmunologyreview03 medical and health sciencesEARLY-LIFEYoung AdultrhinitisAllergy ; Asthma ; Atopic Dermatitis ; RhinitisHypersensitivityJournal Articlemedia_common.cataloged_instanceAnimalsHumansEuropean unionAsthmaMOUNTAIN CEDAR POLLINOSISbusiness.industryGene Expression ProfilingCHILDHOOD ASTHMAAllergensImmunoglobulin Emedicine.diseaseallergyAsthma030104 developmental biology030228 respiratory systemImmunologybiology.proteinImmunizationbusinessGenome-Wide Association Study

description

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.

yearjournalcountryeditionlanguage
2017-02-01Journal of Allergy and Clinical Immunology
10.1016/j.jaci.2016.12.940https://doi.org/10.1016/j.jaci.2016.12.940