AbstractBackgroundIgE‐epitope profiling can accurately diagnose clinical peanut allergy.ObjectiveWe 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.MethodsSixty 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.ResultsIn 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.ConclusionsAccurate 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.