A recent study has uncovered significant links between the success of peanut oral immunotherapy and the immune response in the gastrointestinal tract. Researchers utilized multi-omics profiling to identify molecular factors that influence how children respond to this treatment. The findings suggest that a specific imbalance in immune responses may contribute to the varying effectiveness of peanut immunotherapy.
Aleix Arnau-Soler, PhD, a postdoctoral scientist at the Max-Delbrück-Center for Molecular Medicine, led the study alongside fellow researchers. They noted a critical imbalance between regulatory T-cell responses and B-cell suppression in some patients, contrasted with dominant innate immune signaling and signs of metabolic stress. This imbalance could explain why certain children do not achieve complete desensitization to peanuts during therapy.
The U.S. Food and Drug Administration approved peanut oral immunotherapy, known as Palforzia, in January 2020. While this treatment is effective for many, it is estimated that between 15% and 30% of patients remain at risk of severe allergic reactions, including anaphylaxis, due to inadequate response.
In this study, researchers conducted a placebo-controlled trial involving 49 children (29 boys, 20 girls; mean age of 7 years) diagnosed with peanut allergies confirmed through challenges. Of these participants, 27 received the peanut treatment while 22 were given a placebo, with 11 switching from placebo to treatment later. The active group underwent a gradual dose escalation to achieve a target dose of 125–250 mg of peanut protein, maintained for an additional two months.
Analysis revealed that those who fully responded to the treatment, tolerating up to 4500 mg of peanut protein (equivalent to approximately 15–30 peanuts), exhibited lower levels of peanut-specific IgE and Th2 cytokines such as IL-4 and IL-5 before treatment. In contrast, incomplete responders could tolerate only up to 1000 mg of peanut protein.
The research team identified 184 differentially expressed genes and 1001 differentially methylated genes associated with immune cell types, including innate lymphoid cells and various T-cell subsets. These findings underscore the importance of gastrointestinal immune regulation in determining the effectiveness of oral immunotherapy.
Researchers highlighted that children with gastrointestinal symptoms showed specific immune signatures, including increased presence of regulatory T cells and certain T-cell responses. This suggests that inflammation in gut tissues plays a vital role in the success of the treatment.
The study also found that patients undergoing peanut oral immunotherapy exhibited significantly lower activity of immunoglobulin genes compared to those receiving a placebo. This indicates a potential alteration in B-cell functionality due to the therapy. Among those who responded positively, there was an observed enhancement in regulatory T-cell activity, along with suppression of B-cell responses. Conversely, incomplete responders demonstrated prevailing innate immune signaling and signs of metabolic stress.
In an accompanying editorial, Annette Kuehn, PhD, from the Luxembourg Institute of Health, and Thomas Eiwegger, MD, from the University of Toronto, emphasized the relevance of these findings in understanding gut-associated immunity. They noted, “A limitation is that those findings are confirmed at the protein and single-cell level.” They called for future studies to integrate various omics approaches to explore both innate and adaptive immune responses in the context of oral immunotherapy.
The study, titled “Understanding the Variability of Peanut-Oral Immunotherapy Responses by Multi-Omics Profiling of Immune Cells,” was published online on July 22, 2025. As peanut allergies continue to pose significant health risks for children worldwide, this research offers valuable insights into optimizing treatment approaches and improving outcomes for affected individuals.
