Alexandra F. Santos, MD, MSc

Credit: King's College London

Basophil activation test (BAT) is the most useful biomarker in terms of predicting severity and allergic reaction threshold to baked egg (BE), according to recent findings, and may be advantageous in the management of allergy to eggs.¹

The study’s investigators noted that while consumption of baked egg is associated with an improved prognosis, if patients with allergies do not—at the time of diagnosis—consume baked egg or only consume in miniscule amounts, there may then be a need for risk assessment regarding introduction into the patient’s diet as well as the best setting.²

The investigators sought to address such concerns regarding allergic patients’ potential for severe reactions, and they did so by working toward identifying biomarkers which could then be utilized for clinical decisions.

This new research was led by Alexandra F. Santos, MD, MSc, from the Department of Women and Children's Health (Pediatric Allergy) at the King's College London School of Life Course Sciences in the UK.

“In this study, we analyzed demographic, clinical and immunologic characteristics of BAT2 study participants who reacted to baked egg and loosely cooked egg during double-blind placebo-controlled food challenges (DBPCFC) to identify biomarkers of severity of allergic reactions and of low threshold dose of reactivity,” Santos and colleagues wrote.

Background and Findings

The investigators prospectively recruited individuals from the BAT2 study, specifically from specialized tertiary Pediatric Allergy clinics found in the city of London. The reeferrals given to the investigators from several different clinicians then were followed by a screening telephone assessment designed to confirm participant eligibility, with prior approval obtained from the Sponsor, the UK Health Research Authority, and the Research Ethics Committee.

Informed consent was provided by adults with parental responsibility, and children older than 7 years offered assent. The study focused on children aged 6 months to 15 years who underwent clinical assessment, skin prick tests, blood sample collection for serology and basophil activation tests (BAT), and oral food challenges (OFC) to baked egg. Those who passed the OFC to baked egg subsequently underwent OFC to loosely cooked egg. Food frequency questionnaires and 7-day food diaries were completed by their parents. Subsequently, analyses related to biomarker prediction were restricted to participants with a positive OFC.

The research team’s work involved several different procedures, and these included skin prick tests with raw egg, egg extract, and baked egg slurry, as well as the measurement of total IgE and the specificIgG4 and IgE levels to egg-related antigens. Additionally, they used the BAT with egg extract or baked egg white being utilized as stimulants.

The investigators ensured that each and every one of the participants were given double-blind, placebo-controlled food challenges (DBPCFC) using baked egg, with the exception being infants that were younger than 12 months old who had undergone open OFC to baked eggs.

The research team classified the severity of allergic reactions in real-time through the use of the Practall guidelines, and the threshold dose was defined as the cumulative tolerated dose at the time of the onset of an allergic reaction, in addition to other valuable clinical data they had found.

Out of the team’s 150 children, they found that 40% showed reactions to baked egg, although 21% were shown to have reacted to LCE at the time of the DBPCFC. Among the individuals shown to be challenged with baked egg, the team found that 38% reported more severe reactions and 55% were shown to have sensitivity to smaller levels of egg protein and were, consequently, stratified in the ‘low threshold’ arm.

The investigators’ comparisons of clinical, demographic, and many immunological elements ended up showing no major distinctions between severe/non-severe baked egg reactors or those in the low/high threshold arms of the study. Despite this, the team found that those with severe reactions to baked egg had higher ovomucoid-sIgE levels as well as stronger BAT responses to the product.

Conversely, the investigators found that those who had lower thresholds ended up showing higher IgE-specific activity and BAT reactivity to eggs but lower overall scores for severity. They also noted that optimal cut-off values for finding severe reactors were shown to have been 35% specificity, 100% sensitivity, and 60% accuracy for ovomucoid-sIgE, and 74% specificity, 76% sensitivity, and 75% accuracy for the BAT.

In a similar vein, the research team reported that optimal cut-off values for finding the low-threshold individuals were shown to be 68% specificity, 70% sensitivity, and 69% accuracy for specific activity, and 72% specificity, 70% sensitivity, and 71% accuracy for the BAT.

“Given the multitude of fac-tors that can influence the severity of allergic reaction, decision should not be made on BAT alone but rather in combination with other elements, in the wider context of the patient in question,” they wrote.

References

1. ^{Radulovic, S, Foong, R-X, Bartha, I, et al. Basophil activation test as predictor of severity and threshold of allergic reactions to egg. Allergy. 2023; 00: 1-13. doi:10.1111/all.15875.}
2. ^{Leonard SA, Sampson HA, Sicherer SH, et al. Dietary baked egg accelerates resolution of egg allergy in children. J Allergy Clin Immunol. 2012; 130(2): 473-480.e1.}