Oral immunotherapy directs systemic transcriptomic changes in children with hen’s egg allergy

Background: Hen’s egg (HE) is a major food allergen in children. Oral immunotherapy (OIT) has emerged as a promising therapeutic option for hen’s egg allergy (HEA), but the precise immunological mechanisms underlying HE-OIT are not fully understood. Objective: We aimed to investigate the systemic immune phenotype in children with HEA and to examine transcriptomic changes during HE-OIT. Methods: We enrolled 16 children, aged between 3 and 12 years, diagnosed with HEA (median age, 4.5 years). Peripheral blood mononuclear cells were collected before the initiation of HE-OIT and after the completion of the build-up phase. The transcriptomics of the samples were analyzed using single-cell RNA sequencing. Results: All eight patients (8/8) whose blood samples were collected after the build-up phase achieved desensitization to 60 g of boiled HE white (6.0 g of HE proteins). Following the OIT build-up phase, significant reductions in total CD4⁺ T cells and early activated CD4⁺ T cell were observed (P = 0.001 and 0.045, respectively), while the frequencies of late activated CD4⁺ T cells and fully activated CD8⁺ T cells were increased (P = 0.019 and 0.038, respectively). Clonal analysis revealed proliferation within the late activated CD8⁺ T cell subset following OIT, indicative of the exhausted state of CD8⁺ T cells. Additionally, the population of regulatory T cells with abundant IKZF2 expression was significantly increased after the OIT build-up phase. Conclusion: HE-OIT was associated with systemic immune cell transcriptomic changes, suggesting that its efficacy derives from these immune alterations.