We previously reported the results of a randomized, open-label trial of egg oral immunotherapy (OIT) in 50 children where 44% were desensitized and 46% were partially desensitized after 8 months of treatment. Here we focus on cell-mediated molecular mechanisms driving desensitization during egg OIT. We sought to determine whether changes in genome-wide gene expression in blood cells during egg OIT correlate with humoral responses and the clinical outcome. The blood cell transcriptome of 50 children receiving egg OIT was profiled using peripheral blood mononuclear cell (PBMC) samples obtained at baseline and after 3 and 8 months of OIT. We identified 467 differentially expressed genes (DEGs) after 3 or 8 months of egg OIT. At 8 months, 86% of the DEGs were downregulated and played a role in the signaling of TREM1, IL-6, and IL-17. In correlation analyses, Gal d 1–4-specific IgG4 antibodies associated positively with DEGs playing a role in pathogen recognition and antigen presentation and negatively with DEGs playing a role in the signaling of IL-10, IL-6, and IL-17. Desensitized and partially desensitized patients had differences in their antibody responses, and although most of the transcriptomic changes were shared, both groups had also specific patterns, which suggest slower changes in partially desensitized and activation of NK cells in the desensitized group. OIT for egg allergy in children inhibits inflammation and activates innate immune responses regardless of the clinical outcome at 8 months. Changes in gene expression patterns first appear as posttranslational protein modifications, followed by more sustained epigenetic gene regulatory functions related to successful desensitization.

No abstract

Background Milk oral immunotherapy (OIT) may increase the amount of milk protein that can be ingested without triggering an allergic reaction. It is important to understand why some patients benefit from the treatment while others do not. Objective The aim was to define the differences in the milk allergen component‐specific (casein, α‐lactalbumin, ß‐lactoglobulin) immunoglobulin (sIg [sIgE, sIgG4, and sIgA]) levels relative to the long‐term outcomes of milk OIT. Methods In this long‐term, open‐label follow‐up study, 286 children started milk OIT between 2005 and 2015. Follow‐up data were collected at two points: the post‐buildup phase and long term (range 1–11 years, median 6 years). Comparisons of sIg levels were made among three outcome groups of self‐reported long‐term milk consumption (high‐milk dose, low‐milk dose, and avoidance). Results A total of 168 (59%) of the 286 patients on OIT participated. Most patients (57%) were in the high‐dose group; here, 80% of these patients had a baseline casein sIgE value less than 28 kUA/L, they had the lowest casein sIgE levels at all time (p < .001), their casein sIgG4/IgE levels increased, and long‐term casein sIgA was highest compared with the low‐dose and avoidance groups (p = .02). Low‐milk dose group had the highest casein sIgG4/IgE levels in long term (p = .002). Conclusion The baseline Ig profiles and responses to milk OIT differed depending on long‐term milk consumption. Lower casein sIgE levels were associated with better outcome. Milk casein sIgA differed in the long term among high‐milk consumers.