The role of casein-specific IgA and TGF-β in children with food protein-induced enterocolitis syndrome to milk

Abstract

Background: Food protein-induced enterocolitis syndrome (FPIES) is a gastrointestinal hypersensitivity disorder with a poorly understood pathophysiology and no biomarkers to aid in diagnosis.

Objective: To investigate humoral and cellular responses to casein in children with milk-FPIES, including the role of casein-specific (cs) IgA and T-cell mediated TGF-β responses.

Patients and methods: Thirty-one children previously diagnosed with milk-FPIES were challenged with milk. Twelve age-matched children with FPIES to other foods and 6 milk-tolerant children without a history of FPIES were used as controls. Casein-specific IgE, IgG, IgG4, and IgA were measured in serum and TGF-β levels in supernatants of casein-stimulated PBMCs.

Result: Twenty-six children with milk-FPIES reacted (active milk-FPIES) and five tolerated milk (milk-FPIES resolved) during food challenge. All of them had significantly lower levels of csIgG, csIgG4, and csIgA than control children (p-value<0.001). There were no TGF-β responses in supernatants of active milk-FPIES children.

Conclusion: Children with milk-FPIES have low levels of csIgG, csIgG4, and csIgA. In particular, children with active FPIES to cow's milk have deficient T-cell mediated TGF-β responses to casein, rendering TGF-β a promising biomarker in identifying children who are likely to experience FPIES reactions to this allergen. Prospective studies are needed to validate these findings, elucidate their role in FPIES pathophysiology, and establish the diagnostic utility of TGF-β in milk-induced FPIES.

Keywords: IgA; IgG4; PBMCs; TGF-β; casein; food challenge; immunoglobulin A; milk allergy; peripheral blood mononuclear cell; transforming growth factor β.