Ingestion of egg white after acquisition of oral tolerance with heated egg white in OVA-sensitized mice caused severe allergic symptoms

Heated eggs have often been used for oral immunotherapy of egg allergy because of their lower allergenicity than raw eggs. Furthermore, recent guidelines recommend the earlier introduction of well-cooked eggs to the diet as a supplementary food and protective measure against food allergy in infants. However, the influence of cooking with heat on the allergenicity and tolerogenicity of egg white (EW) antigen in individuals with egg allergy is not well understood. We investigated this by feeding ovalbumin (OVA)-sensitized inbred mice EW heated at 80°C for 15 min (80EW), 100°C for 5 min (100EW), or 121°C for 40 min (121EW). Only 100EW resolved enteritis, and it produced more effective tolerogenicity to OVA than EW. The state of enteritis and tolerogenicity for 80EW was almost the same as that for EW. Th1 responses to short-term feeding were observed with 121EW. We then investigated allergy recurrence after continuous feeding with the 100EW diet. Of note, however, the oral tolerance acquired with 100EW or EW was not effective against allergic recurrence in response to EW, because of residual high levels of serum OVA-specific IgE and residual infiltrated mast cells in the intestine. Furthermore, the recurrence of allergic symptoms in response to EW was more severe when oral tolerance was acquired with 100EW rather than with EW. Our results suggest that patients must be careful not to inadvertently consume EW, even if clinical tolerance to heat-treated EW has been achieved.