Infants with Food Protein-Induced Enterocolitis Syndrome (FPIES) Can Be Classified Into Two Distinct Subgroups Based On the Presence or Absence of Bloody Stool and Their Antigen-Specific Cytokine Production Profiles


      Food protein-induced enterocolitis syndrome (FPIES) is characterized by repeated vomiting upon ingestion of certain food antigens, especially cow’s milk. We recently established a nationwide online database for patients with non-IgE-mediated food allergies and found that some patients exhibit both vomiting and bloody stool. To date, the latter have never been reported in papers regarding FPIES from Western countries. In the present study, we tried to clarify whether FPIES with bloody stool (FPIESwBS) is simply a more severe form of FPIES without bloody stool (FPIESnoBS) or has a different pathogenesis from FPIESnoBS. Clinical and laboratory data and the antigen-specific cytokine secretion profiles were compared between patients with FPIESwBS and patients with FPIESnoBS.


      This study enrolled 115 patients with FPIES (FPIESwBS: n=65; FPIESnoBS: n=50) who fulfilled at least three of Powell’s criteria. Peripheral mononuclear cells were cultured with 100 μg/ml of five lipopolysaccharide-depleted milk protein components separately (α-lactalbumin, β-lactoglobulin, α-casein, β-casein and κ-casein). Lymphoproliferation and the cytokine production profiles were determined by 3H-thymidine-uptake and by Multiplex assay, respectively.


      The clinical symptoms and laboratory data were similar between FPIESwBS and FPIESnoBS, except for the age at onset and disease prognosis. Although the milk protein-specific lymphoproliferative responses and proinflammatory cytokine (TNF-α, IL-6 and IL-1b) levels were similar in both groups, the Th1 (IFN-γ) and Th2 (IL-13 and IL-5) cytokine levels were significantly higher in FPIESwBS than in FPIESnoBS.


      FPIESwBS is a distinct subgroup of patients from FPIESnoBS based on their antigen-specific cytokine production profiles.