Egg therapy reprograms children’s immunity, raising both promise and concern

For decades, children with egg allergies in Korea have lived by avoidance, with their parents instructed to ban eggs from the house, pack special meals for school and carry EpiPens for the accidents that inevitably come. 

A new study from Seoul National University Bundang Hospital (SNUBH) suggests that may no longer be the only option. 

Researchers say oral immunotherapy, or OIT, not only raised children’s tolerance to eggs but also reprogrammed their immune cells in ways that hint at deeper, systemic change.

The trial, published in the Asian Pacific Journal of Allergy and Immunology, enrolled 16 children between the ages of 3 and 12 with IgE-mediated egg allergy. Treatment began with minute doses of boiled egg white, which were increased stepwise under supervision. 

By the end of the build-up phase, 15 children reached the desensitization threshold, able to consume 60 grams of boiled egg white -- about the equivalent of one egg -- without allergic symptoms during challenge tests. One child developed anaphylaxis, a severe and potentially life-threatening allergic reaction, and dropped out, a reminder that the therapy carries real risks.

What set this work apart was not only the clinical result but also the molecular readout. Using single-cell RNA sequencing, the researchers profiled more than 106,000 immune cells before and after therapy. 

They saw significant reductions in early-activated CD4+ T cells, which are key drivers of acute allergic flares, alongside increases in late-activated CD4+ cells, fully activated CD8+ T cells showing features of exhaustion, and natural regulatory T cells marked by Helios, which are thought to stabilize immune tolerance.

“This was not just desensitization,” said Professor Jang Se-heun of pediatrics at SNUBH, who led the study, in an interview with Korea Biomedical Review last Friday. “We could see immune reprogramming at the transcriptomic level,” a signal, he added, that oral immunotherapy may alter the disease course rather than simply mute symptoms.

The single dropout provided a warning sign of its own. The child who experienced anaphylaxis showed high expression of NR4A2 in fully activated CD8+ cells before therapy, a gene tied in animal studies to mast cell activation. While far from definitive, Jang suggested such signals could become biomarkers for identifying children at higher risk of severe reactions.

Other markers looked more encouraging. Children whose egg-specific IgG4 -- sometimes called a blocking antibody -- rose during therapy tended to show stronger tolerance. Reductions in early-activated CD4+ cells may also indicate a positive response. The journal authors wrote that these changes “may serve as potential biomarkers for monitoring treatment response,” though they cautioned that larger studies are needed.

Durability remains the unanswered question. The children in the study kept eating eggs four times a week for a median of 27 months, maintaining their tolerance. Whether that tolerance will persist without ongoing exposure, the so-called sustained unresponsiveness, is still unknown. “We don’t yet know how long daily dosing must continue to reach that stage,” Jang said.

The stakes in Korea are considerable. Egg allergy affects an estimated 0.25 percent of children, according to the study, and unlike peanuts, eggs are woven into everyday diets. “Once you start banning eggs, you are banning too many foods,” Jang said, noting that the quality-of-life impact on children and parents is far larger than statistics alone suggest.

Other tools are emerging. Biologics such as omalizumab, marketed by Genentech and Novartis as Xolair, are designed to bind IgE antibodies in the blood and blunt allergic reactions. The drug is FDA-approved in the United States to reduce reactions to accidental food exposures, including eggs, and can be used alone or with OIT. 

In a U.S. government-funded trial presented in March, Xolair helped 36 percent of highly sensitive multi-food allergy patients tolerate at least 2 grams of peanut protein and two other allergens, compared with 19 percent who received oral immunotherapy alone. The drug works by binding IgE antibodies and preventing them from arming mast cells, which trigger reactions.

Jang acknowledged biologics’ promise but was cautious. “Cost is a factor, yes, and also the fact that biologics are not yet approved in Korea for this purpose,” he said. “If biologics become cheaper and more widely available, they could become a standard option. But at this point, oral immunotherapy is the more effective and practical approach.”

Other candidates, such as dupilumab and investigational anti–IL-33 drugs, are being studied as stand-alone treatments or as adjuncts to OIT. For now, though, OIT remains the most widely studied approach, even as its risks spark debate over whether waiting for natural resolution of egg allergy may be safer for some children.