A new study has identified key factors that influence the effectiveness of peanut oral immunotherapy (OIT) in children, highlighting the role of gut immune responses. Conducted by a team led by Aleix Arnau-Soler, PhD, at the Max-Delbrück-Center, the research employs multi-omics profiling of immune cells to uncover molecular mechanisms associated with different responses to treatment.
Published findings suggest that an imbalance between regulatory T-cell (Treg) responses and B-cell suppression may lead to incomplete desensitization in some patients. The study emphasizes that while peanut OIT, marketed as Palforzia, received approval from the US Food and Drug Administration in January 2020, approximately 15% to 30% of patients remain at risk for severe allergic reactions, including anaphylaxis.
To explore these dynamics, the researchers conducted a placebo-controlled trial involving 49 children diagnosed with a peanut allergy. Participants were divided into two groups: 27 children received peanut protein, while 22 children were given a placebo, with some later switching to the active treatment. Over a period of 14 months, those in the active group underwent dose escalation, ultimately reaching a target dose of 125–250 mg of peanut protein.
The study results indicated that those classified as complete responders—children who tolerated 4500 mg of peanut protein—had significantly lower levels of peanut-specific immunoglobulin E (IgE) and Th2 cytokines (such as IL-4 and IL-5) compared to incomplete responders, who could manage only ≤ 1000 mg of peanut protein.
Through multi-omics profiling, investigators identified 184 differentially expressed genes and 1001 differentially methylated genes linked to immune cell types, including innate immune cells and specific subsets of T cells. These findings highlight the critical role of gastrointestinal immune regulation in the success of peanut OIT.
Researchers observed that children experiencing gastrointestinal symptoms showed distinct immune signatures in their gut, characterized by increased levels of Th2 cells and memory Tregs. These findings point to the important interplay between gut health and allergic responses.
In contrast, incomplete responders demonstrated heightened innate immune signaling and metabolic stress, suggesting that these factors may hinder the efficacy of therapy. The study revealed that participants receiving peanut OIT exhibited significantly lower activity of immunoglobulin genes compared to those on placebo, indicating a shift in B-cell functionality due to treatment.
In an accompanying editorial, Annette Kuehn, PhD, from the Luxembourg Institute of Health, and Thomas Eiwegger, MD, from the University of Toronto, praised the research for providing deeper insights into the immune mechanisms at play. They noted the potential for future studies to integrate advanced transcriptomic methods with traditional allergen-specific stimulation approaches.
The authors of the study concluded that while their findings shed light on the complex nature of gut-associated immunity in effective peanut OIT, further research is necessary. They recommended confirming these results at the protein and single-cell level and urged researchers to consider the overall balance of gut immunity when examining immunological changes during OIT.
This groundbreaking work not only advances the understanding of peanut allergies but also opens new avenues for improving treatment strategies for affected children.