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Background Accurate diagnosis of peanut allergy is a significant clinical challenge. Here, a novel diagnostic blood test using the peanut bead-based epitope assay ("peanut BBEA") was developed utilizing the LEAP cohort and then validated using two independent cohorts. Methods The development of the peanut BBEA diagnostic test followed the National Academy of Medicine's established guidelines with discovery performed on 133 subjects from the non-interventional arm of the LEAP trial and an independent validation performed on 82 subjects from the CoFAR2 and 84 subjects from the POISED study. All samples were analyzed using the peanut BBEA methodology, which measures levels of IgE to two Ara h 2 sequential (linear) epitopes and compares their combination to a threshold pre-specified in the model development phase. When a patient has an inconclusive outcome by skin prick testing (or sIgE), IgE antibody levels to this combination of two epitopes can distinguish whether the patient is "Allergic" or "Not Allergic." Diagnoses of peanut allergy in all subjects were confirmed by double-blind placebo-controlled food challenge and subjects' ages were 7-55 years. Results In the validation using CoFAR2 and POISED cohorts, the peanut BBEA diagnostic test correctly diagnosed 93% of the subjects, with a sensitivity of 92%, specificity of 94%, a positive predictive value of 91%, and negative predictive value of 95%. Conclusions In validation of the peanut BBEA diagnostic test, the overall accuracy was found to be superior to existing diagnostic tests for peanut allergy including skin prick testing, peanut sIgE, and peanut component sIgE testing.

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B cells in human food allergy have been studied predominantly in the blood. Little is known about IgE+ B cells or plasma cells in tissues exposed to dietary antigens. We characterized IgE+ clones in blood, stomach, duodenum, and esophagus of 19 peanut-allergic patients, using high-throughput DNA sequencing. IgE+ cells in allergic patients are enriched in stomach and duodenum, and have a plasma cell phenotype. Clonally related IgE+ and non-IgE-expressing cell frequencies in tissues suggest local isotype switching, including transitions between IgA and IgE isotypes. Highly similar antibody sequences specific for peanut allergen Ara h 2 are shared between patients, indicating that common immunoglobulin genetic rearrangements may contribute to pathogenesis. These data define the gastrointestinal tract as a reservoir of IgE+ B lineage cells in food allergy.

Trends in egg specific immunoglobulin levels during natural tolerance and oral immunotherapy

Details about IgE-producing B cells in the gut in the context of food allergy are scarce, despite the frequent exposure of the gut and its associated lymphoid tissues to dietary antigens. A new study finds that IgE-producing B cells are enriched in gut tissues and are probably generated from local antibody isotype switching.

The prevalence of food allergies has been on the increase over the last 2 decades. Diagnosing food allergies can be complicated, as there are multiple types that have distinct clinical and immunologic features. Food allergies are broadly classified into immunoglobulin E (IgE)-mediated, non-IgE-mediated, or mixed food allergic reactions. This review focuses on the clinical manifestations of the different categories of food allergies and the different tests available to guide the clinician toward an accurate diagnosis.

Background Thirty percent of children with food allergies have multiple simultaneous allergies; however, the features of these multiple allergies are not well characterized serologically or clinically. Objective We comprehensively evaluated 60 multifood-allergic patients by measuring serum IgE to key allergen components, evaluating clinical histories and medication use, performing skin tests, and conducting double-blind, placebo-controlled food challenges (DBPCFCs). Methods Sixty participants with multiple food allergies were characterized by clinical history, DBPCFCs, total IgE, specific IgE, and component-resolved diagnostics (IgE and IgG4) data. The food allergens tested were almond, egg, milk, sesame, peanut, pecan, walnut, hazelnut, cashew, pistachio, soy, and wheat. Results Our data demonstrate that of the reactions observed during a graded DBPCFC, gastrointestinal reactions occurred more often in boys than in girls, as well as in individuals with high levels of IgE to 2S albumins from cashew, walnut, and hazelnut. Certain food allergies often occurred concomitantly in individuals (ie, cashew/pistachio and walnut/pecan/hazelnut). IgE testing to components further corroborated serological relationships between and among these clustered food allergies. Conclusions Associations of certain food allergies were shown by DBPCFC outcomes as well as by correlations in IgE reactivity to structurally related food allergen components. Each of these criteria independently demonstrated a significant association between allergies to cashew and pistachio, as well as among allergies to walnut, pecan, and hazelnut.

Introduction Oral food challenges (OFCs) are considered the gold standard of diagnosing food allergy. Repeat food challenges are necessary to assess if food allergies are persistent or outgrown. Methods A retrospective chart review was conducted on all clinical protocols initiated at our institution involving standardized screening OFCs. Analysis was performed among participants who were challenged to the same food twice at variable time points. Repeat challenges were available for 8 food allergens. Allergic reactions were assessed by modified Bock's criteria and ranked in order of severity. Results Twenty-eight participants repeated challenges to the same allergen once or twice for a total of 65 challenges. Forty-two positive challenges corresponding to 18 participants were analyzed. Peanut had the largest number of repeat challenges (n=19 participants), followed by almond (n=4), milk, walnut and egg (n=2), cashew, hazelnut, and sesame (n=1). Among the positive challenges, sixteen repeat challenges were conducted to peanut, two to egg, and one each to almond, milk, and walnut. In participants with a repeat positive food challenge, the eliciting dose (ED) did not change (p=0.66), but reactions were more severe (p=0.02). Change in either ED or severity rank was not associated with time between repeat challenges (p=0.94 and p = 0.56, respectively). Additionally, our analysis showed that symptoms varied widely during subsequent challenges. Conclusions Our findings show increased severity with variable allergic reactions between OFCs, regardless of the duration of time between challenges. Larger cohorts are needed to validate these preliminary findings.

Introduction Improved biomarkers predictive of food challenge thresholds are needed. Methods A retrospective chart review was performed on IRB-approved clinical protocols where standardized screening oral food challenges (OFCs) to a cumulative dose of 500 mg protein were conducted to any of 11 potential food allergens. Dose-dependent receiver operating characteristic (ROC) curves for specific IgE (sIgE), sIgE/total IgE ratio (sIgEr), and skin prick test (SPT) were generated to determine optimal allergen-specific biomarker thresholds predictive of OFC outcome adjusting for cumulative tolerated dose (CTD). Results A total of 1274 OFCs completed by 427 participants were analyzed. The majority of food-specific SPT, sIgE, and sIgEr thresholds calculated from the CTD-dependent ROC curves were highly predictive of OFC outcome [area under the curves (AUCs) > 0.75]. Participants with values above the thresholds were more likely to have a positive challenge and react at lower doses compared to those with values below (p Conclusions These reported SPT, sIgE, and sIgEr threshold values appear highly predictive of challenge outcome and may serve as a substitute for food challenges in the appropriate setting.

Background Basophil activation tests (BATs) have promise for research and for clinical monitoring of patients with allergies. However, BAT protocols vary in blood anticoagulant used and temperature and time of storage before testing, complicating comparisons of results from various studies. Objective We attempted to establish a BAT protocol that would permit analysis of blood within 24 hours of obtaining the sample. Methods Blood from 46 healthy donors and 120 patients with peanut allergy was collected into EDTA or heparin tubes, and samples were stored at 4°C or room temperature for 4 or 24 hours before performing BATs. Results Stimulation with anti-IgE or IL-3 resulted in strong upregulation of basophil CD203c in samples collected in EDTA or heparin, stored at 4°C, and analyzed 24 hours after sample collection. However, a CD63 hi population of basophils was not observed in any conditions in EDTA-treated samples unless exogenous calcium/magnesium was added at the time of anti-IgE stimulation. By contrast, blood samples collected in heparin tubes were adequate for quantification of upregulation of basophil CD203c and identification of a population of CD63 hi basophils, irrespective of whether the specimens were analyzed by means of conventional flow cytometry or cytometry by time-of-flight mass spectrometry, and such tests could be performed after blood was stored for 24 hours at 4°C. Conclusion BATs to measure upregulation of basophil CD203c and induction of a CD63 hi basophil population can be conducted with blood obtained in heparin tubes and stored at 4°C for 24 hours.