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| Item Type: | Article |
|---|---|
| Title: | Understanding the variability of peanut-oral immunotherapy responses by multi-omics profiling of immune cells |
| Creators Name: | Arnau-Soler, Aleix, Ashley, Sarah E., Ghauri, Ahla, Jeanrenaud, Alexander C.S.N., Marenholz, I., Blumchen, Katharina, Cibin, Penelope, Iakupova, Alisa, Hubner, Norbert, Beyer, Kirsten and Lee, Young-Ae |
| Abstract: | BACKGROUND: Oral immunotherapy (OIT) induces desensitization in peanut allergy, yet 15%-30% of patients do not respond, and a significant risk of anaphylaxis due to treatment remains. In a placebo-controlled peanut OIT trial, this study identifies molecular drivers of OIT responsiveness through multi-omics profiling in immune cells. METHODS: Immunoglobulins, cytokines, transcriptome, and DNA methylome profiles were analyzed in peanut-stimulated and unstimulated peripheral blood mononuclear cells isolated from peanut-allergic children before and after treatment. Multi-omics profiling focused on OIT responsiveness within the active treatment arm. Additional subgroup analyses were performed to further elucidate molecular mechanisms and potential biomarkers. RESULTS: Complete responders, tolerating 4500 mg of peanut protein, exhibited lower pre-treatment peanut-specific IgE and Th2 cytokine production (IL-4, IL-5) compared to incomplete responders who tolerated ≤ 1000 mg of peanut protein after treatment. Our primary analysis identified 184 differentially expressed genes and 1001 differentially methylated genes, enriched for innate (ILC3) and adaptive (CD8αα subset of CD8(+) T cells) immune cells, alongside γδ T cells and exosomes, highlighting gastrointestinal regulatory processes as central to OIT success. We found a marked downregulation of immunoglobulin genes in patients receiving peanut compared to placebo, suggesting OIT-induced modulation of B-cell activity. Functional networks revealed a marked imbalance contrasting regulatory T-cell responses and B-cell suppression in the complete responders with innate immune signaling and metabolic stress in the incomplete responders. CONCLUSION: This multi-omics approach underscores the importance of gastrointestinal immune mechanisms underlying the variation in peanut oral immunotherapy responses and offers potential biomarkers for improving treatment strategies. |
| Keywords: | Biomarkers, DNA Methylome, Oral Immunotherapy, Peanut Allergy, Transcriptome |
| Source: | Allergy |
| ISSN: | 0105-4538 |
| Publisher: | Wiley |
| Page Range: | 1-17 |
| Date: | 22 July 2025 |
| Official Publication: | https://doi.org/10.1111/all.16627 |
| PubMed: | View item in PubMed |
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