Patterns of IgE responses to multiple allergen components and clinical symptoms at age 11 years.

BACKGROUND: The relationship between sensitization to allergens and disease is complex. OBJECTIVE: We sought to identify patterns of response to a broad range of allergen components and investigate associations with asthma, eczema, and hay fever. METHODS: Serum specific IgE levels to 112 allergen components were measured by using a multiplex array (Immuno Solid-phase Allergen Chip) in a population-based birth cohort. Latent variable modeling was used to identify underlying patterns of component-specific IgE responses; these patterns were then related to asthma, eczema, and hay fever. RESULTS: Two hundred twenty-one of 461 children had IgE to 1 or more components. Seventy-one of the 112 components were recognized by 3 or more children. By using latent variable modeling, 61 allergen components clustered into 3 component groups (CG1, CG2, and CG3); protein families within each CG were exclusive to that group. CG1 comprised 27 components from 8 plant protein families. CG2 comprised 7 components of mite allergens from 3 protein families. CG3 included 27 components of plant, animal, and fungal origin from 12 protein families. Each CG included components from different biological sources with structural homology and also nonhomologous proteins arising from the same biological source. Sensitization to CG3 was most strongly associated with asthma (odds ratio [OR], 8.20; 95% CI, 3.49-19.24; P < .001) and lower FEV1 (P < .001). Sensitization to CG1 was associated with hay fever (OR, 12.79; 95% CI, 6.84-23.90; P < .001). Sensitization to CG2 was associated with both asthma (OR, 3.60; 95% CI, 2.05-6.29) and hay fever (OR, 2.52; 95% CI, 1.38-4.61). CONCLUSIONS: Latent variable modeling with a large number of allergen components identified 3 patterns of IgE responses, each including different protein families. In 11-year-old children the pattern of response to components of multiple allergens appeared to be associated with current asthma and hay fever but not eczema.

Pediatric asthma and development of atopy.

PURPOSE OF REVIEW: There is ongoing controversy about the relationship between atopy and asthma. RECENT FINDINGS: In clinical practice, specific IgE and skin test results should not be reported as 'positive' or 'negative', but as the level of IgE and the size of skin test wheal diameter. In assessment of children with severe asthma, these tests are not mutually exclusive but complementary, and both should be carried out and quantified. In the near future, their diagnostic accuracy in children with wheezing may be improved by the measurement of allergen-specific IgG. It is becoming increasingly clear that asthma is not a single disease, but a collection of several diseases with similar/same symptoms. These distinct disease entities (endotypes) may share similar observable characteristics (phenotypes), but arise via different pathophysiological mechanisms. Observable phenotypic features (e.g. sputum inflammatory phenotypes) are not stable in children with asthma. The discovery of novel, latent endotypes of asthma will require integration of a time component to take into account the phenotype instability and longitudinal changes. Not only asthma, but also 'atopy' encompasses a number of different endotypes which differ in their association with asthma. SUMMARY: Novel endotypes of atopy and asthma which better reflect the unique pathophysiological processes underlying different diseases in the atopy and asthma syndromes can be defined through the fusion of computational thinking and novel mathematical approaches with biomedical science. These novel endotypes may be more relevant for epidemiological, genetic and therapeutic studies.