HAZELNUT allergy was associated with molecular changes involving immune regulation, vitamin D metabolism and epithelial barrier genes, according to a new study.
By integrating DNA methylation, gene expression and protein data, researchers identified biological signals that could provide new directions for understanding the condition.
Researchers compared immune cell profiles from 24 individuals with oral food challenge-confirmed hazelnut allergy and 109 nonallergic controls.
Researchers analysed DNA methylation, gene expression and secreted proteins in immune cells, both before and after exposure to hazelnut protein. Across the analyses, they identified 87 differentially methylated signatures, 125 unique differentially expressed genes and 11 unique differentially secreted proteins associated with hazelnut allergy.
Findings highlighted changes in genes associated with ZNF341 and ARL2, which the researchers linked to STAT3-mediated immunoglobulin E (IgE) dysregulation.
A hypermethylated region overlapping TH2LCRR was also identified, suggesting a potential epigenetic mechanism contributing to increased interleukin (IL)-5 and IL-13 expression.
Antigen stimulation revealed hazelnut-specific transcriptional and protein signals. Integrated analysis showed that IL-5 expression could distinguish allergic from nonallergic individuals, while broader molecular patterns indicated activation of innate immune responses involving antimicrobial, antiviral and cytokine-mediated inflammatory pathways.
Researchers also identified increased activity in the vitamin D pathway, involving CYP27B1 and IL32, alongside methylation signals in epithelial barrier genes associated with the gut and skin, including TRIM31, TRIM40 and CDSN.
The study provides a detailed molecular profile of hazelnut allergy and identifies several potential areas for further investigation. However, researchers highlighted limitations, including the small sample size, differences in age between allergic and nonallergic participants, and the use of peripheral blood mononuclear cells, which limited cell-specific analysis.
Researchers concluded that larger studies are needed to confirm and extend these findings, with the identified molecular signals providing candidate biomarkers for future mechanistic research and prospective validation.
Reference
Jeanrenaud ACSN et al. Multi-Omics Analysis Reveals Vitamin D Metabolism, Hyper-IgE Genes, and Epithelial Barrier Dysfunction in Hazelnut Allergy. Allergy. 2026;DOI: 10.1111/all.70525.
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