Specific IgG₄ antibodies to cow's milk proteins in pediatric patients with eosinophilic esophagitis

Background: Allergen-specific IgG₄ (sIgG₄) antibodies are often associated with tolerance, but sIgG₄ antibodies to causally relevant foods have been reported recently in adults with eosinophilic esophagitis (EoE). Prevalence and levels of food sIgG₄ are not well established in the general pediatric population.

Objective: We sought to investigate serum food sIgG₄ with component diagnostics in children with EoE and children from an unselected birth cohort and to explore the effects of sex, age, and milk consumption on sIgG₄ levels.

Methods: Sera from 71 pediatric patients with EoE and 210 early adolescent children from an unselected birth cohort (Project Viva) were assayed for sIgG₄ and specific IgE (sIgE) to major cow's milk (CM) proteins (α-lactalbumin, β-lactoglobulin, and caseins) and to wheat, soy, egg, and peanut proteins.

Results: In the EoE cohort high-titer sIgG₄ (≥10 μg/mL) to CM proteins was more common than in control sera and achieved odds ratios for EoE ranging from 5.5 to 8.4. sIgE levels to CM proteins were mostly 4 IU/mL or less in patients with EoE, such that sIgG₄/sIgE ratios were often 10,000 or greater. When adjusted for age and milk consumption, high-titer sIgG₄ to CM proteins was strongly associated with EoE, with an odds ratio of greater than 20 to all 3 CM proteins in boys.

Conclusions: sIgG₄ to CM proteins are common and high titer in children with EoE. Although it is not clear that this response is pathogenic, sIgG₄ levels imply that these antibodies are an important feature of the local immune response that gives rise to EoE.