Study Links Hazelnut Allergy to Vitamin D and Immune Gene Changes

Hazelnut allergy involves distinct molecular changes across immune regulation, vitamin D metabolism, and epithelial barrier genes, according to a new study.

The immune cell profiles of 24 people with an oral food challenge-verified hazelnut allergy were evaluated against those of 109 nonallergic control participants. Following this, the investigators evaluated gene expression, DNA methylation, and secreted proteins within immune cells both prior to and after hazelnut protein exposure.

Across the analyses, investigators identified 87 differentially methylated signatures, 125 unique differentially expressed genes, and 11 unique differentially secreted proteins associated with the allergy. These findings map the biological signals underlying the condition to provide new directions for clinical understanding.

The study highlights changes in genes associated with ZNF341 and ARL2, which researchers linked to STAT3-mediated immunoglobulin E, or IgE, dysregulation. A hypermethylated region overlapping TH2LCRR was also identified, suggesting an epigenetic mechanism that contributes to increased interleukin-5 and interleukin-13 expression.

Antigen stimulation revealed hazelnut-specific transcriptional and protein signals. Through combined analysis, the data demonstrated that interleukin-5 levels could successfully separate allergic subjects from nonallergic ones, whereas wider molecular trends pointed to innate immune activation encompassing inflammatory, antiviral, antimicrobial, and cytokine-driven pathways.

Investigators also identified increased activity in the vitamin D pathway involving CYP27B1 and IL32. Alongside these changes, methylation signals appeared in epithelial barrier genes associated with the gut and skin, including TRIM31, TRIM40, and CDSN.

By outlining the molecular characteristics of hazelnut allergies, the research uncovers multiple avenues that warrant additional study. Nevertheless, the authors pointed out several constraints, such as a limited cohort size, disparities in age among the allergic and nonallergic subjects, and the reliance on peripheral blood mononuclear cells that restricted cell-type resolution.

The study’s authors said that bigger trials must be conducted to validate and build upon these discoveries, noting that the discovered molecular signatures serve as prospective biomarkers for upcoming mechanistic studies and validation efforts.