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

Jean Christoph Caubet, Ramon Bencharitiwong, Andrew Ross, Hugh A. Sampson, M. Cecilia Berin, Anna Nowak-Węgrzyn*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


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 TH2 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.

Original languageEnglish (US)
Pages (from-to)572-583
Number of pages12
JournalJournal of Allergy and Clinical Immunology
Issue number2
StatePublished - Feb 1 2017


  • allergy
  • food
  • Food protein–induced enterocolitis syndrome
  • humoral response
  • non–IgE-mediated
  • T1 response
  • T2 response
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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