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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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Karisola, Palosuo, Hinkkanen, Wisgrill, Savinko, Fyhrquist, Alenius and Mäkelä.)

Hypersensitivity to the chicken egg is a widespread disorder mainly affecting 1-2% of children worldwide. It is the second most common food allergy in children, next to cow's milk allergy. Egg allergy is mainly caused by hypersensitivity to four allergens found in the egg white; ovomucoid, ovalbumin, ovotransferrin and lysozyme. However, some research suggests the involvement of allergens exclusively found in the egg yolk such as chicken serum albumin and YGP42, which may play a crucial role in the overall reaction. In egg allergic individuals, these allergens cause conditions such as itching, atopic dermatitis, bronchial asthma, vomiting, rhinitis, conjunctivitis, laryngeal oedema and chronic urticaria, and anaphylaxis. Currently there is no permanent cure for egg allergy. Upon positive diagnosis for egg allergy, strict dietary avoidance of eggs and products containing traces of eggs is the most effective way of avoiding future hypersensitivity reactions. However, it is difficult to fully avoid eggs since they are found in a range of processed food products. An understanding of the mechanisms of allergic reactions, egg allergens and their prevalence, egg allergy diagnosis and current treatment strategies are important for future studies. This review addresses these topics and discusses both egg white and egg yolk allergy as a whole., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Evidence of the efficacy of food oral immunotherapy (OIT) is not robust enough to change clinical practice from current standard management. Furthermore, the immunologic changes underlying food desensitization are unknown., Objective: To establish the immunologic basal status and differences between an egg-allergic group of children and a population of nonallergic children and to investigate the safety and efficacy of a specific egg OIT protocol to induce clinical desensitization and the associated immune responses., Methods: Children with or without egg allergy were recruited. Allergic subjects underwent an OIT protocol based on weekly doses of egg protein and a maintenance phase. Immune profile and changes in all subjects were investigated by measuring T-helper cells types 1 and 2 (TH1 and TH2) and T-regulatory cytokines and transcription factors and egg-specific IgE and IgG4 levels., Results: At baseline, a significantly lower production of ovalbumin-specific interleukin (IL)-10 and tumor necrosis factor-α and a trend toward higher IL-5 and IL-13 were found in allergic children. The egg OIT protocol enabled 60% of them to ingest 32 mL of egg white. Significant increases in egg-specific IgG4 levels and IL-10 production, with a trend toward lower IL-5 and IL-13 and higher tumor necrosis factor-α and interferon-γ levels, and significant decreases in egg-specific IgE concentration were observed., Conclusion: Egg-allergic individuals display a bias toward TH2 type cytokine production and decreased TH1 and IL-10 responses compared with nonallergic individuals. The OIT protocol was safe and effective in inducing egg desensitization, leading to a shift in the immune profile of allergic individuals toward a nonallergic phenotype., (Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Observational studies suggest that early regular ingestion of allergenic foods might reduce the risk of food allergy., Objective: We sought to determine whether early regular oral egg exposure will reduce subsequent IgE-mediated egg allergy in infants with moderate-to-severe eczema., Methods: In a double-blind, randomized controlled trial infants were allocated to 1 teaspoon of pasteurized raw whole egg powder (n = 49) or rice powder (n = 37) daily from 4 to 8 months of age. Cooked egg was introduced to both groups after an observed feed at 8 months. The primary outcome was IgE-mediated egg allergy at 12 months, as defined based on the results of an observed pasteurized raw egg challenge and skin prick tests., Results: A high proportion (31% [15/49]) of infants randomized to receive egg had an allergic reaction to the egg powder and did not continue powder ingestion. At 4 months of age, before any known egg ingestion, 36% (24/67) of infants already had egg-specific IgE levels of greater than 0.35 kilounits of antibody (kUA)/L. At 12 months, a lower (but not significant) proportion of infants in the egg group (33%) were given a diagnosis of IgE-mediated egg allergy compared with the control group (51%; relative risk, 0.65; 95% CI, 0.38-1.11; P = .11). Egg-specific IgG4 levels were significantly (P < .001) greater in the egg group at both 8 and 12 months., Conclusion: Induction of immune tolerance pathways and reduction in egg allergy incidence can be achieved by early regular oral egg exposure in infants with eczema. Caution needs to be taken when these high-risk infants are first exposed to egg because many have sensitization already by 4 months of age., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Hen's egg allergy affects young children and can cause severe allergic reactions. Avoidance results in dietary limitations and can affect the quality of life, especially in cases where potentially life-threatening reactions exist. Our objective was to desensitize children with moderate-severe IgE-mediated hen's egg allergy over a 6-month period, by introducing increasing and very gradual daily doses of raw hen's egg in order to enable the children to assume 25ml of this food, or to induce tolerance to the highest possible dose. The protocol foresaw the egg reintroduction in the home setting., Methods: In this randomized, controlled open study, 20 hen's egg allergic children (10 in the active group) were admitted. A convincing history or a positive double-blind placebo-controlled food challenge confirmed the diagnosis. Oral desensitization was performed with increasing doses starting from 0.27 mg of hen's egg proteins (1 drop of raw hen's egg diluted 1:100). We adopted an original, mathematically calculated protocol in order to ensure a constant, daily increment of doses., Results: 8/10 children (80%) in the active group achieved the daily intake of 25ml over a 6-month period. One child (10%) could tolerate up to 2ml/day while another child (10%) failed the desensitization. Six months after enrolment only 2 children in the control group (20%) could tolerate hen's egg., Conclusions: We successfully desensitized 8/10 children with IgE-mediated hen's egg allergy in a 6-month period. The partial outcome in the child who could tolerate 2ml/day reduced the risk of severe reactions after unnoticed introduction of egg. A regular protocol that ensures a daily constant increase of doses helps to reduce possible adverse events, thus improving safety and effectiveness., (© 2012 John Wiley & Sons A/S.)

Purpose of Review: Egg allergy is one of the most common food allergies of childhood and no interventional therapy is currently approved by the Food and Drug Administration. Much recent research has focused on the safety, efficacy, and mechanism of oral immunotherapy (OIT) as a disease-modifying treatment., Recent Findings: Small pilot studies with varying protocol designs have shown egg OIT to be relatively well tolerated, and efficacy is suggested but not formally demonstrated. At this time, no placebo-controlled randomized trial has been published confirming desensitization and no published study has convincingly demonstrated the development of OIT-induced tolerance to egg., Summary: Egg OIT is a promising modality for providing temporary protection from reactions caused by accidental egg exposure. However, the overall strength of the evidence in favor of egg OIT is limited by small sample sizes and the lack of controls, both of which are important considerations given the spontaneous resolution expected in egg allergy. More high-quality studies are necessary before egg OIT can be recommended as a viable treatment option.

Objective: The goal was to assess the effectiveness of specific immunotherapy (SIT) in reduction of symptoms and medication score in patients with immunoglobulin E (IgE) mediated extrinsic form of atopic dermatitis (AD); and to assess the effectiveness of oral immunotherapy (OIT) as "active" treatment to achieving tolerance for food(s) in patients with IgE mediated food allergy., Data Sources: Computerized bibliographic searches of MEDLINE (1998-2010) were supplemented by hand searches of reference lists. Studies were included if they were double-blind randomized controlled trials comparing subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT) or OIT with placebo. However uncontrolled studies and case reports were also included., Study Selections: Thirty-two studies were analyzed. Because of the high heterogeneity of the AD studied only results of 2 placebo controlled studies 1-SCIT and 1-SLIT respectively were comparable. Among OIT studies: 4 carried out with control groups were analyzed., Results: From 36% to 92% of patients treated with OIT reached tolerance to cow's milk or egg; a rate of 8% to 53% reached partial tolerance. The patients had either clinical history of severe systemic reactions to foods: anaphylaxis, or mild to moderate reactions. Regarding SIT for AD: 72% of patients treated with house dust mite SCIT and 54% treated with SLIT had a significant improvement of SCORAD-Index., Conclusions: This review found that OIT with cow's milk or egg is effective in achieving full tolerance or partial tolerance in the majority of patients with IgE mediated food allergy. SIT may represent an additional therapeutic tool for the treatment of extrinsic AD in properly selected patients., (Copyright © 2011 American College of Allergy. Published by Elsevier Inc. All rights reserved.)

Background: Hen's egg allergy is among the most common food allergies in childhood and predicts later development of allergic disease. The optimal efficacy and mechanism(s) of egg allergen immunotherapy are poorly understood., Objective: To enhance immunologic and clinical outcomes of egg oral immunotherapy (OIT) using a conditionally increased dosing strategy., Methods: In an open-label clinical trial of egg OIT, egg-allergic children ingested daily doses of egg protein that were gradually increased based on the egg white (EW) IgE level. Skin prick test reactivity and EW- and ovomucoid-specific cellular and humoral responses were measured longitudinally. To confirm clinical tolerance, patients underwent double-blinded, placebo-controlled food challenges 1 month after completing the dosing protocol., Results: Children aged 3 to 13 years with characteristics of clinical egg allergy were enrolled. All 6 patients who completed the entire protocol developed clinical tolerance to egg during the study. The median wheal diameter on EW skin prick testing decreased from 10 to 2.5 mm during OIT (P = .03). Both EW and ovomucoid IgE levels significantly decreased during the study (median EW IgE level: from 18.8 kU/L at baseline to 3.9 kU/L, P = .03), and corresponding IgG4 levels increased (median EW IgG4 level: from 0.65 mg/L at baseline to 86.15 mg/L, P = .03). Transient increases were seen in egg-induced interleukin 10 (P = .06) and transforming growth factor β (P = .18) levels, and the ratio of T(H)2:T(H)1 cytokine production was decreased (P = .25)., Conclusions: Egg OIT is associated with tolerance acquisition in children with persistent egg allergy. Individualized dosing regimens may be necessary to achieve a full therapeutic effect in some patients., (Copyright © 2010 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)