Specific IgG4 Antibodies to Cow’s Milk Proteins in Pediatric Patients With Eosinophilic Esophagitis

Abstract

Although food protein causes eosinophilic esophagitis (EoE), the mechanism is not clear and appears not to be immunoglobulin E (IgE)–mediated. Cow’s milk (CM) is among the most common causal foods in patients with EoE. Specific immunoglobulin G4 (sIgG4) antibodies to food extracts, including CM, have been found in sera and esophageal biopsies of adults with EoE. Is this true in children with EoE?This study included data from 71 pediatric patients with EoE and 210 pediatric control subjects from an unselected birth cohort (Project Viva).Sera were assayed for sIgG4 and specific IgE to major CM proteins (α-lactalbumin, β-lactoglobulin, and caseins) as well as to wheat, soy, egg, and peanut.In the EoE cohort, elevated levels of sIgG4 (>10 mg/mL) to CM proteins were more common than in control sera (odds ratios: 5.5–8.4). When adjusted for age and milk consumption, high-titer sIgG4 to CM proteins was strongly associated with EoE (odds ratios: 21.2–23.9 in boys and 2.7–9.3 in girls).Elevated levels of sIgG4 to CM proteins are common in children with EoE. Although the clinical relevance of these elevated levels it is not clear, results suggest that sIgG4 levels may be an important factor in EoE.The 2 currently accepted treatments for EoE are medical (swallowed corticosteroids to coat the esophagus) and dietary (elimination of foods and serial endoscopies to evaluate response). Although medical therapy is generally safe, it is likely required indefinitely. Although dietary therapy has the appeal of avoiding medication, it requires repeated endoscopies and does not always identify a culprit food or foods and also likely requires lifelong food avoidance. There is a striking correlation between EoE and other atopic diseases (asthma, allergic rhinitis, atopic dermatitis, and especially food allergy), yet specific IgE to food proteins does not identify culprit EoE foods or appear to be involved in the pathogenesis of this condition. As the authors note, the correlation between sIgG4 to CM proteins and EoE does not prove a causal relationship but may instead be an epiphenomenon. Indeed, in other settings, sIgG4 is associated with food tolerance, such as with successful desensitization in children undergoing oral immunotherapy for IgE-mediated CM allergy. Nonetheless, the association is intriguing and warrants further investigation to help understand how food causes EoE and whether a blood test could be developed to identify causal foods.