The immune mystery of Food Protein Induced Enterocolitis Syndrome (FPIES)


Published Online: March 4, 2015

Food protein-induced enterocolitis syndrome, or FPIES, is a food allergy that occurs in infancy. Milk is the most common trigger of FPIES, but other common triggers of FPIES include soy, rice, and oats. Ingestion of the food results in a characteristic set of symptoms including profuse vomiting and shock-like symptoms (pallor, lethargy) beginning two hours after exposure. In a recent article in The Journal of Allergy and Clinical Immunology (JACI), Berin et al review the literature to summarize the current state of knowledge about the immune mechanisms of FPIES.

The understanding of how the immune system causes symptoms in FPIES lags far behind the knowledge about IgE-mediated food allergies like peanut allergy. There is specificity in FPIES reaction, in that individuals react reproducibly to certain foods but not others, and individuals can be reactive to one, two, or many foods. Studies performed over 40 years ago showed that infants with milk-FPIES had reactions when they were fed with purified protein components of milk, supporting the conclusion that it is the protein component of the food that triggers symptoms. There are two ways that the immune system uses to recognize foreign proteins: antibodies and T cell receptors. As reviewed in the paper, there is a lack of compelling evidence for a contribution of either antibodies or lymphocytes in FPIES. However, there is clear evidence that cells of the immune system are activated by ingestion of the triggering food in those with symptoms. Cells of the innate immune system, including neutrophils, eosinophils, and platelets change their distribution in the blood. Stool extracts obtained from individuals with symptoms after exposure to the food show signs of inflammation, and prolonged exposure to the triggering food in the diet results in inflammation and structural changes in the small intestine. We do not yet understand how these cells of the innate immune system get activated by food proteins.

The most compelling piece of information that is unknown in FPIES is how foods are specifically recognized in the intestine. Major roadblocks to new discoveries in FPIES are (1) the lack of access to gastrointestinal tissue for research because biopsies are not necessary for patient care, and (2) the lack of an appropriate animal model.

Comprehensive immune profiling of patients with active versus outgrown FPIES is needed to advance our understanding of the immune basis of these mysterious adverse reactions to foods, and may provide insight into novel ways that the immune system can recognize foreign proteins.


The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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