Suppression of established IgE-mediated food allergy with anti-FcεRIα mAb (HYP7P.310)

Abstract

Abstract Food allergy, in mouse models, is mediated by mast cells, FcεRI and IgE. We recently demonstrated that rapid desensitization with a hamster mAb to mouse FcεRIα (MAR-1) safely suppresses IgE-mediated anaphylaxis (JACI, 131:1555-64, 2013). Consequently, we evaluated whether the same approach could suppress established food allergy in BALB/c mice that had been sensitized intraperitoneally with ovalbumin/alum or egg white/alum and challenged repeatedly by oral gavage with ovalbumin or egg white until they had developed shock and diarrhea. Treatment of these mice with 50 µg of MAR-1 every 4 days suppressed both the induction of hypothermia by oral gavage with ovalbumin or egg white and mast cell MMCP1 secretion by 85-90% and decreased the incidence of diarrhea by 70-85%. Although MAR-1 suppression of food allergy was eventually limited by mouse development of IgG antibodies to hamster IgG, this could be prevented by injecting mice with anti-CD4 mAb (GK1.5) at the time of the initial MAR-1 injection. Although GK1.5, by itself, had little effect on established food allergy, the combination of MAR-1 plus GK1.5 completely suppressed the hypothermia, diarrheal, MMCP1, IL-4 and IL-13 responses to oral gavage with ovalbumin or egg white. These observations suggest that rapid desensitization, followed by continuing treatment with a non-immunogenic (humanized) anti-FcεRIα mAb might effectively suppress IgE-mediated food allergy in people with this disorder.