Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Simpson A

PROVIDER: S-EPMC4649774 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Simpson Angela A Lazic Nevena N Belgrave Danielle C M DC Johnson Phil P Bishop Christopher C Mills Clare C Custovic Adnan A

The Journal of allergy and clinical immunology 20150430 5

<h4>Background</h4>The relationship between sensitization to allergens and disease is complex.<h4>Objective</h4>We sought to identify patterns of response to a broad range of allergen components and investigate associations with asthma, eczema, and hay fever.<h4>Methods</h4>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 pat ...[more]

PMID: 25935108

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Project description:BackgroundCross-reactive carbohydrate determinant (CCD) structures found in plant and insect glycoproteins are commonly recognized by IgE antibodies as epitopes that can lead to extensive cross-reactivity and obscure in vitro diagnostic (IVD) serology results. With the introduction of component resolved diagnosis (CRD), recombinant non-glycosylated components have been utilized to mitigate the risk of CCD-specific IgE (sIgE) detection. However, a recent study has shown that CCD-sIgE may bind directly to the cellulose solid phase matrix used in certain in vitro diagnostic assays, eliminating the advantage of CRD over traditional extract-based testing. The aim of this study is to further investigate the prevalence of CCD-sIgE interference on a commonly-used in vitro sIgE automated platform which employs a cellulose-based matrix to immobilize CCD-free recombinant components.MethodsSera from patients sensitized to peanut, silver birch, and/or timothy grass were analyzed for CCD-sIgE reactivity on ImmunoCAP/Phadia and NOVEOS autoanalyzers against the MUXF3 carbohydrate component. Positive CCD-sIgE sera were further analyzed against non-glycosylated recombinant components bound to the ImmunoCAP solid phase in the absence and presence of a soluble CCD inhibitor. For comparison, sera were then analyzed on NOVEOS, a non-cellulose based automated sIgE assay.ResultsSera from 35% of the sensitized population tested in this study were positive (≥0.35 kU/L) for CCD-sIgE. Of those positives, 17% resulted in CCD-sIgE-positive (false positive) results on ImmunoCAP using non-glycosylated allergosorbents that were negative on NOVEOS. Sera producing false-positive results on ImmunoCAP had varying levels of CCD-sIgE from 0.67 kU/L to 36.52 kU/L. The incidence of CCD interference was predominantly delimited to low-positive IgE results (0.35 kUA/L- 3.00 kUA/L).ConclusionFalsely elevated diagnostic allergen-sIgE results can commonly occur due to the presence of CCD-sIgE using assays that employ a carbohydrate matrix-based allergosorbent. Even the use of non-glycosylated recombinant allergenic components coupled to cellulose matrices do not reduce their risk of detection. The risk of CCD interference that compromises quantitative IgE results can be mitigated by the addition of a soluble CCD inhibitor to positive CCD-sIgE containing sera or by alternatively using a non-cellulose based sIgE assay, such as the NOVEOS assay.

Project description:BackgroundSerum inhibition of allergen-specific IgE has been associated with competing IgG4 and non-specific polyclonal IgE. In allergen immunotherapy, beneficial responses have been associated with high IgG4/IgE ratios. Helminths potentiate antibody class switching to IgG4 and stimulate polyclonal IgE synthesis; therefore, we hypothesized a role for helminth-associated IgG4 and total IgE in protection against atopic sensitization and clinical allergy (asthma) in tropical low-income countries.MethodsAmong community residents of Ugandan rural Schistosoma mansoni (Sm)-endemic islands and a mainland urban setting with lower helminth exposure, and among urban asthmatic schoolchildren and non-asthmatic controls, we measured total, Schistosoma adult worm antigen (SWA)-specific, Schistosoma egg antigen (SEA)-specific and allergen (house dust mite [HDM] and German cockroach)-specific IgE and IgG4 by ImmunoCAP® and/or ELISA. We assessed associations between these antibody profiles and current Sm infection, the rural-urban environment, HDM and cockroach skin prick test (SPT) reactivity, and asthma.ResultsTotal IgE, total IgG4 and SWA-, SEA- and allergen-specific IgE and IgG4 levels were significantly higher in the rural, compared to the urban setting. In both community settings, both Sm infection and SPT reactivity were positively associated with allergen-specific and total IgE responses. SPT reactivity was inversely associated with Schistosoma-specific IgG4, allergen-specific IgG4/IgE ratios and total IgE/allergen-specific IgE ratios. Asthmatic schoolchildren, compared with non-asthmatic controls, had significantly higher levels of total and allergen-specific IgE, but lower ratios of allergen-specific IgG4/IgE and total IgE/allergen-specific IgE.Conclusions and clinical relevanceOur immuno-epidemiological data support the hypothesis that the IgG4-IgE balance and the total IgE-allergen-specific IgE balance are more important than absolute total, helminth- or allergen-specific antibody levels in inhibition of allergies in the tropics.

Dataset Information

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

Background

Objective

Methods

Results

Conclusions

Publications

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

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