Dataset Information

Development of a tool predicting severity of allergic reaction during peanut challenge.

ABSTRACT:

Background

Reliable prognostic markers for predicting severity of allergic reactions during oral food challenges (OFCs) have not been established.

Objective

To develop a predictive algorithm of a food challenge severity score (CSS) to identify those at higher risk for severe reactions to a standardized peanut OFC.

Methods

Medical history and allergy test results were obtained for 120 peanut allergic participants who underwent double-blind, placebo-controlled food challenges. Reactions were assigned a CSS between 1 and 6 based on cumulative tolerated dose and a severity clinical indicator. Demographic characteristics, clinical features, peanut component IgE values, and a basophil activation marker were considered in a multistep analysis to derive a flexible decision rule to understand risk during peanut of OFC.

Results

A total of 18.3% participants had a severe reaction (CSS >4). The decision rule identified the following 3 variables (in order of importance) as predictors of reaction severity: ratio of percentage of CD63^hi stimulation with peanut to percentage of CD63^hi anti-IgE (CD63 ratio), history of exercise-induced asthma, and ratio of forced expiratory volume in 1 second to forced vital capacity (FEV₁/FVC) ratio. The CD63 ratio alone was a strong predictor of CSS (P < .001).

Conclusion

The CSS is a novel tool that combines dose thresholds and allergic reactions to understand risks associated with peanut OFCs. Laboratory values (CD63 ratio), along with clinical variables (exercise-induced asthma and FEV₁/FVC ratio) contribute to the predictive ability of the severity of reaction to peanut OFCs. Further testing of this decision rule is needed in a larger external data source before it can be considered outside research settings.

Trial registration

ClinicalTrials.gov identifier: NCT02103270.

SUBMITTER: Chinthrajah RS

PROVIDER: S-EPMC6026554 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

Development of a tool predicting severity of allergic reaction during peanut challenge.

Chinthrajah R Sharon RS Purington Natasha N Andorf Sandra S Rosa Jaime S JS Mukai Kaori K Hamilton Robert R Smith Bridget Marie BM Gupta Ruchi R Galli Stephen J SJ Desai Manisha M Nadeau Kari C KC

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 20180427 1

<h4>Background</h4>Reliable prognostic markers for predicting severity of allergic reactions during oral food challenges (OFCs) have not been established.<h4>Objective</h4>To develop a predictive algorithm of a food challenge severity score (CSS) to identify those at higher risk for severe reactions to a standardized peanut OFC.<h4>Methods</h4>Medical history and allergy test results were obtained for 120 peanut allergic participants who underwent double-blind, placebo-controlled food challenges ...[more]

PMID: 29709643

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Project description:BackgroundUnexpected allergic reactions to peanut are the most common cause of fatal food-related anaphylaxis. Mechanisms underlying the variable severity of peanut-allergic reactions remain unclear.ObjectivesWe sought to expand mechanistic understanding of reaction severity in peanut allergy.MethodsWe performed an integrated transcriptomic and epigenomic study of peanut-allergic children as they reacted in vivo during double-blind, placebo-controlled peanut challenges. We integrated whole-blood transcriptome and CD4+ T-cell epigenome profiles to identify molecular signatures of reaction severity (ie, how severely a peanut-allergic child reacts when exposed to peanut). A threshold-weighted reaction severity score was calculated for each subject based on symptoms experienced during peanut challenge and the eliciting dose. Through linear mixed effects modeling, network construction, and causal mediation analysis, we identified genes, CpGs, and their interactions that mediate reaction severity. Findings were replicated in an independent cohort.ResultsWe identified 318 genes with changes in expression during the course of reaction associated with reaction severity, and 203 CpG sites with differential DNA methylation associated with reaction severity. After replicating these findings in an independent cohort, we constructed interaction networks with the identified peanut severity genes and CpGs. These analyses and leukocyte deconvolution highlighted neutrophil-mediated immunity. We identified NFKBIA and ARG1 as hubs in the networks and 3 groups of interacting key node CpGs and peanut severity genes encompassing immune response, chemotaxis, and regulation of macroautophagy. In addition, we found that gene expression of PHACTR1 and ZNF121 causally mediates the association between methylation at corresponding CpGs and reaction severity, suggesting that methylation may serve as an anchor upon which gene expression modulates reaction severity.ConclusionsOur findings enhance current mechanistic understanding of the genetic and epigenetic architecture of reaction severity in peanut allergy.

Project description:BackgroundThe management of peanut allergy relies on allergen avoidance and epinephrine autoinjector for rescue treatment in patients at risk of anaphylaxis. Biomarkers of severity and threshold of allergic reactions to peanut could significantly improve the care for patients with peanut allergy.ObjectiveWe sought to assess the utility of the basophil activation test (BAT) to predict the severity and threshold of reactivity to peanut during oral food challenges (OFCs).MethodsThe severity of the allergic reaction and the threshold dose during OFCs to peanut were determined. Skin prick tests, measurements of specific IgE to peanut and its components, and BATs to peanut were performed on the day of the challenge.ResultsOf the 124 children submitted to OFCs to peanut, 52 (median age, 5 years) reacted with clinical symptoms that ranged from mild oral symptoms to anaphylaxis. Severe reactions occurred in 41% of cases, and 57% reacted to 0.1 g or less of peanut protein. The ratio of the percentage of CD63(+) basophils after stimulation with peanut and after stimulation with anti-IgE (CD63 peanut/anti-IgE) was independently associated with severity (P = .001), whereas the basophil allergen threshold sensitivity CD-sens (1/EC?? × 100, where EC?? is half maximal effective concentration) value was independently associated with the threshold (P = .020) of allergic reactions to peanut during OFCs. Patients with CD63 peanut/anti-IgE levels of 1.3 or greater had an increased risk of severe reactions (relative risk, 3.4; 95% CI, 1.8-6.2). Patients with a CD-sens value of 84 or greater had an increased risk of reacting to 0.1 g or less of peanut protein (relative risk, 1.9; 95% CI, 1.3-2.8).ConclusionsBasophil reactivity is associated with severity and basophil sensitivity is associated with the threshold of allergic reactions to peanut. CD63 peanut/anti-IgE and CD-sens values can be used to estimate the severity and threshold of allergic reactions during OFCs.

Dataset Information

Development of a tool predicting severity of allergic reaction during peanut challenge.

Background

Objective

Methods

Results

Conclusion

Trial registration

Publications

Development of a tool predicting severity of allergic reaction during peanut challenge.

Similar Datasets

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