Rush Oral Immunotherapy Does Not Reduce Allergic Response in Mice with Mild Allergy to Egg White Ovomucoid

Abstract

Summary Oral immunotherapy (OIT) is a promising therapeutic approach for treating food allergy. Past studies have shown that OIT reduces allergic response only in severe allergy model mice. We worked to establish mild allergy model mice, and investigated whether 'rush' OIT for 10 d improved the allergic response and biomarkers in these mice. Balb/c mice were sensitized to ovomucoid (OM) in alum. The rush OIT was done for 10 d. Oral OM challenge was used to determine the impact of OIT on the allergic response. We measured allergic biomarkers, such as vascular permeability in the skin, plasma levels of total IgE, OM-specific IgE, IgG1 and IgG2a and cytokines in splenocyte culture supernatant. OIT for 10 d did not improve allergy symptoms and increased vascular permeability. Total IgE in the plasma of OIT-treated mice was significantly higher than in that of non-treated mice. OM-specific IgG1 and IgG2a plasma levels were not significantly different between OIT-treated and non-treated mice. Among the cytokine secretion of splenocyte from OITtreated mice, IFN-g and IL-10 were significantly lower than in non-treated mice, and IL-4 and IL-5 were significantly higher. Total TGF-b in the OIT-treated group was not detected. The IFN-g/IL-4 ratio of the OIT-treated group was about 1/8 that of the non-treated group. OIT for 10 d was not effective and some biomarkers showed negative responses in the mild allergy model mice. We suggest OIT should be used very carefully as this treatment carries a risk of worsening allergy symptoms for mice with mild allergy. Key Words oral immunotherapy, food allergy, allergy model mice Food allergies affect about 3% of the overall population and up to 4-6% of children (1-3). In recent times, the prevalence of reported food allergy has increased 18% among children under 18 y of age (2, 3). Dietary avoidance of specific allergens is recommended as the first-line approach in the management of food allergy (1, 2). Recently, oral immunotherapy (OIT) has been studied as a new treatment for food allergy (2,4,5). OIT uses small amounts of food allergen to desensitize the patient. However, OIT is not often recommended because it carries the risk of increasing allergy symptoms (2, 6).In Japan, egg allergy has been reported as the most prevalent food hypersensitivity in the pediatric population, exceeding cow's milk allergy (7). Ovalbumin (OVA) and ovomucoid (OM) were identified as egg white allergen epitopes, constituting about 54 and 11% of egg white protein, respectively (8,9). OM is heat resistant and has high allergenicity (10, 11). It is a well-known trypsin inhibitor (8). This suggested that OIT for OM (egg)-specific allergy patients may be a highly effective treatment and a pathway to allergen tolerance.As research in this area has been limited, there is inadequate evidence to establish proper OIT protocols, such as allergen dosage, escalation, duration of therapy and method of administration (2). OIT protocols are categorized as either 'slow' or 'rush.' In slow OIT, the allergen dose is increas...

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“…However, according to the Japanese pediatric guidelines for food-allergy treatment, OIT is not often recommended because of the risk of inducing the allergic symptoms during the treatment (4). Moreover, current data are inadequate to establish proper OIT protocols, such as allergen dose and timing, need for escalation, therapy duration, and routes of administration.There are some reports of the OIT protocol in an allergic mouse model (8)(9)(10)(11)(12). We propose a new OIT regimen that involves mixing a small amount of allergen powder in the diet.…”

“…There are some reports of the OIT protocol in an allergic mouse model (8)(9)(10)(11)(12). We propose a new OIT regimen that involves mixing a small amount of allergen powder in the diet.…”