Mechanisms of Development of Allergy

2010 - 2015
Josep M. Antó

Allergic diseases (asthma (A), rhinitis (R) and eczema(E)) are complex and associated with allergen-specific IgE and non-allergic mechanisms that may coexist in the same patient (multimorbidity of A, R & E). MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) was launched to generate novel knowledge on the mechanisms of initiation of allergy from early childhood to young adulthood. MeDALL linked epidemiological, clinical and basic research. It was based on a novel, stepwise, large-scale and integrative approach led by a network of complementary experts in allergy, epidemiology, allergen biochemistry, immunology, molecular biology, epigenetics, functional genomics, bioinformatics, computational and systems biology.

Steps followed

  • Identification of “classical” and “novel” phenotypes in existing birth cohorts
  • Building discovery of the relevant mechanisms in IgE-associated allergic diseases in existing longitudinal birth cohorts;
  • Validation and redefinition of classical and novel phenotypes of IgE-associated allergic diseases, and
  • Translational integration of systems biology outcomes into healthcare, including societal aspects.

Main findings

  • Multimorbidity of A, R & E is more common than expected by chance alone suggesting that the diseases share causal mechanisms.
  • Using unsupervised cluster analysis at 4 and 8 years, two groups were identified suggesting that asthma, rhinitis and eczema can be classified together as an allergic comorbidity cluster.
  • A computational analysis of the topology of the protein interaction network shows that asthma, eczema and rhinitis share a larger number of associated proteins than expected by chance.
  • A targeted proteomic approach allowed to assess the role of several candidates including CC16 and YKl-40 of asthma and allergy related phenotypes in children. Identifying a potential novel biomarker of asthma and the role of systemic inflammation in allergic multimorbidities in early childhood, both using the classical and novel phenotypes.
  • As part of the translational efforts in MeDALL a systematic review of characteristics of risk prediction models to identify preschool children with asthma-like symptoms who will develop clinical asthma at school age. Twelve prediction models were identified.

Total funding:

1,493,456 €

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