Oral tolerance induction does not resolve allergic enteropathy due to residual IgE (125.7)

Abstract

Abstract Oral immunotherapy (OIT) has gained attention as a therapy for food allergies. To investigate efficacy and safety of OIT pre-clinically, we established a murine model of allergic enteropathy. BALB/c mice were sensitised with ovalbumin (OVA, a major egg white allergen) plus ALUM and fed egg-white diet (EW-diet). The mice developed gastrointestinal symptoms (e.g. weight loss) and inflammation in the jejunum accompanied by a strong induction of IgE antibodies during the first 7 days of the allergenic diet. Importantly, the mice presented resolution of the symptoms and remarkable reduction of OVA-specific IgE levels in the sera if they were fed EW-diet more than 7 days. Reduced proliferation of T-cells from spleens and mesenteric lymph nodes of the mice on day 28 of EW-diet indicated that the continuous feeding of the allergenic diet induced oral tolerance. However, the inflammation in the jejunum of the mice was aggravated at this time point. We hypothesized that residual OVA-specific IgE antibodies promoted the intestinal inflammation, although oral tolerance against OVA was induced by the long-term EW diet. To verify it, we used mice deficient of FcϵRI, a high affinity IgE receptor. FcϵRI deficient mice presented intestinal inflammation on day 7 of EW-diet after OVA sensitisation. However, if EW-diet was continued, their intestinal inflammation was resolved. Our results suggest that residual IgE could be a poor prognostic factor for recovery from allergic enteropathy in OIT.