New insights in the understanding of FPIES pathomechanisms


Published Online: August 22, 2016

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. Cow’s milk (CM) and soy proteins are the most common causes, followed by grains (rice and oat), in the USA. The underlying mechanism of FPIES has not been clearly defined and requires further characterization. FPIES is considered to represent the most severe end of the spectrum of the food allergic disorders that predominantly affect the gut. Results from previous studies suggested a central role of a subtype of inflammatory cells and their production of proinflammatory cytokines. However, the evidence is weak and these data need to be confirmed.  

In an article recently published in The Journal of Allergy and Clinical Immunology (JACI), Caubet and colleagues characterized immune responses to one of the major CM allergen (casein) in children with FPIES caused by CM. Both cellular and antibody immune responses were examined. For this purpose, the investigators used blood samples from patients with active CM-FPIES and compared with those with resolved CM-FPIES and those with IgE-mediated CM allergy.

The investigators confirmed the paucity of antibody responses in patients with CM-FPIES. They found lower levels of CM-  and casein-specific-IgG antibodies in patients with CM-FPIES compared to those tolerating CM. T cell activation by casein was similar to that found in controls (children with active and resolved IgE-mediated CM allergy). Interestingly, they found higher serum levels of interleukin-10 in resolved as compared to active CM-FPIES suggesting that IL-10 which is a regulatory cytokine, might play a key role in acquisition of tolerance in patients with CM-FPIES. The investigators also found increased serum IL-8 level which is a potent neutrophil chemotactic factor suggesting neutrophil involvement in the disease. CM-FPIES patients also had higher serum tryptase levels as compared to those with resolved disease suggesting that mast cells might also be involved in the disease. These findings indicate that CM-FPIES is an immunologically complex disease that involves several arms of the immune system.

The Journal of Allergy and Clinical Immunology (JACI) is an official journal of the AAAAI.

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