Regular Allergen Exposure During Oral Immunotherapy Alters the Transcriptomic Innate Immune Response After Cellular Restimulation in Children With Egg Allergy

BACKGROUND AND OBJECTIVE: Oral immunotherapy (OIT) is a promising treatment for food allergies. However, the molecular mechanisms leading to desensitization remain unknown. Objective: To better understand the immunological mechanisms and transcriptional changes underlying desensitization to food allergens during OIT. METHODS: Our cohort consisted of 40 Finnish children with egg allergy who underwent OIT. Peripheral blood mononuclear cells (PBMCs) were collected at 0, 3, and 8 months of therapy and stimulated with an egg allergen extract. Differentially expressed genes (DEGs) were identified based on quantile-normalized and batch-corrected microarray data using a linear model. Gene enrichment and Pearson correlation analyses were conducted. RESULTS: After 8 months of therapy, 45% of patients were fully desensitized and 55% partially desensitized. Stimulation with egg yielded 49 DEGs at 0 months, 723 DEGs at 3 months, and 759 DEGs at 8 months in PBMCs after comparison with unstimulated controls. At 8 months of OIT, allergen stimulation led to down-regulation of proinflammatory pathways, as well as IL-4 and IL-13 signaling. At baseline, the immune response in the fully desensitized group was more reactive than in the partially desensitized group. CONCLUSIONS: During OIT, general immune activity is increased, especially the number of down-regulated genes, suggesting active immune suppression. Transcriptomic profiles differ between fully and partially desensitized patients, with a notably more reactive immune response in the fully desensitized group at baseline. Innate immunity seems to play a significant role in the development of desensitization during OIT.