Increased cow's milk protein–specific IgG4 levels after oral desensitization in 7- to 12-month-old infants

Background Cow's milk protein (CMP)-specific IgG4 responses and the efficacy of oral desensitization in infants with cow's milk allergy (CMA) warrant more clarification. Objective To explore whether CMP-specific IgG4 responses develop during infancy and whether regular CM exposure is efficacious for inducing a CMP-specific IgG4 response accompanying CM desensitization in 7- to 12-month-old infants. Methods CM-specific IgE and CMP (α-lactalbumin, β-lactoglobulin, and casein)-specific IgG4 levels were measured in 262 CM-sensitized children. Of these, 31 infants 7 to 12 months old with challenge-proved CMA were randomly assigned to oral desensitization or an elimination diet and evaluated 6 months later. Results CMP-specific IgG4 levels in 7- to 12-month-old infants were higher than in those younger than 6 months but comparable to those in children older than 12 months. CMP-specific IgG4 levels in 7- to 12-month-old infants with CMA were significantly lower than in those without CMA. Fourteen of 16 patients receiving oral desensitization could accept daily doses of 200 mL of CM, whereas all but 3 dropout patients receiving the elimination diet still showed allergic symptoms at the follow-up food challenge. In patients who became desensitized, CM-specific IgE levels were lower than at baseline, whereas CMP-specific IgG4 levels were significantly increased. In patients receiving the elimination diet, CM-specific IgE and CMP-specific IgG4 levels remained unchanged. Conclusion CMP-specific IgG4 responses did not develop sufficiently in 7- to 12-month-old infants with CMA. Oral desensitization in 7- to 12-month-old infants with CMA was associated with the upregulation of CMP-specific IgG4 responses accompanying the alleviation of CMA symptoms.