Humoral and cellular responses to casein in patients with food protein-induced enterocolitis to cow's milk

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy manifesting within 1 to 4 hours of food ingestion with repetitive emesis and lethargy.

Objective: We sought to characterize immune responses to casein in children with FPIES caused by cow's milk (CM).

Methods: Total IgE and IgM, CM-specific IgG, and casein-specific IgE, IgG, IgG₄, and IgM levels, as well as immunoglobulin free light chains, were measured in both patients with active and those with resolved CM-FPIES. Proliferating casein/T-effector cell counts were measured in children with CM-FPIES, children with IgE-mediated CM allergy, and those tolerating CM. Cytokine concentrations in the supernatants were quantified. Serum cytokine and tryptase levels were measured before and after a positive oral food challenge (OFC) result and compared with levels in those with a negative OFC result.

Results: We found low levels of CM and casein-specific IgG and casein-specific IgG₄ in patients with CM-FPIES versus those tolerating CM (P < .05). Although we found both a high CD4⁺ T cell-proliferative response and T_H2 cytokines production after casein stimulation in children with CM-FPIES, results were similar to those in control subjects. Significantly lower secretion of IL-10 and higher secretion of IL-9 by casein-stimulated T cells were found in patients with CM-FPIES versus those with IgE-mediated CM allergy. Lower baseline serum levels of IL-10 and higher tryptase levels were found in active CM-FPIES versus resolved CM-FPIES. We found a significant increase in serum IL-10 and IL-8 levels after a positive OFC result.

Conclusions: We confirm the paucity of humoral response in patients with CM-FPIES. IL-10 might play a key role in acquisition of tolerance in patients with CM-FPIES. Increased serum IL-8 levels in patients with active FPIES suggest neutrophil involvement. Elevated baseline serum tryptase levels in patients with active FPIES suggest low-grade intestinal mast cell activation or increased mast cell load.