Predicting probability of tolerating discrete amounts of peanut protein in allergic children using epitope‐specific IgE antibody profiling

Abstract

Background IgE‐epitope profiling can accurately diagnose clinical peanut allergy. Objective We sought to determine whether sequential (linear) epitope‐specific IgE (ses‐IgE) profiling can provide probabilities of tolerating discrete doses of peanut protein in allergic subjects undergoing double‐blind, placebo‐controlled food challenges utilizing PRACTALL dosing. Methods Sixty four ses‐IgE antibodies were quantified in blood samples using a bead‐based epitope assay. A pair of ses‐IgEs that predicts Cumulative Tolerated Dose (CTD) was determined using regression in 75 subjects from the discovery cohort. This epitope‐based predictor was validated on 331 subjects from five independent cohorts (ages 4–25 years). Subjects were grouped based on their predicted values and probabilities of reactions at each CTD threshold were calculated. Results In discovery, an algorithm using two ses‐IgE antibodies was correlated with CTDs (rho = 0.61, p < .05); this correlation was 0.51 (p < .05) in validation. Using the ses‐IgE‐based predictor, subjects were assigned into “high,” “moderate,” or “low” dose‐reactivity groups. On average, subjects in the “high” group were four times more likely to tolerate a specific dose, compared with the “low” group. For example, predicted probabilities of tolerating 4, 14, 44, and 144 or 444 mg in the “low” group were 92%, 77%, 53%, 29%, and 10% compared with 98%, 95%, 94%, 88%, and 73% in the “high” group. Conclusions Accurate predictions of food challenge thresholds are complex due to factors including limited responder sample sizes at each dose and variations in study‐specific challenge protocols. Despite these limitations, an epitope‐based predictor was able to accurately identify CTDs and may provide a useful surrogate for peanut challenges.

CD23 + IgG1 + memory B cells are poised to switch to pathogenic IgE production in food allergy

“…The reactivity of the Ara h 2–specific monoclonal antibodies described above was also tested using a sequential linear epitope assay ( 38 , 39 ). We found that all identified members of the 4C5G1 convergent family bound to the same Ara h 2 epitope (Ara h 2.008; fig.…”

An update on recent developments and highlights in food allergy

“…Threshold and severity assessments may also be assisted by biomarkers. The cumulative tolerated dose of allergic reaction was associated with sequential (linear) epitope‐specific IgE profiling 195 . The severity of allergic reactions of children was shown to inversely associate with platelet‐activating factor acetylhydrolase, a stable enzyme that plays a central role in degrading the lipid mediator platelet‐activating factor 196 .…”

“…The cumulative tolerated dose of allergic reaction was associated with sequential (linear) epitope-specific IgE profiling. 195 The severity of allergic reactions of children was shown to inversely associate with platelet-activating factor acetylhydrolase, a stable enzyme that plays a central role in degrading the lipid mediator platelet-activating factor. 196 The management of FA has an ongoing need for refinement of patient selection, dose, regimen, and duration.…”

An update on recent developments and highlights in food allergy

“…The cumulative tolerated dose of allergic reaction was associated with sequential (linear) epitope-specific IgE profiling. 156 The severity of allergic reactions of children was shown to inversely associate with platelet activating factor acetylhydrolase, a stable enzyme that plays a central role in degrading the lipid mediator platelet activating factor. 157 The management of FA has an ongoing need for refinement of patient selection, dose, regimen, and duration.…”