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

Food protein-induced enterocolitis syndrome (FPIES) is a type of food allergy in which children who eat milk, soy, or other foods develop repetitive vomiting and sometimes diarrhea.  This can lead to dehydration, and, in the longer run, failure to thrive.  But unlike more typical food allergies, FPIES isn’t mediated by IgE antibodies.  In fact, what causes FPIES is still a bit of a mystery.  In this month’s issue of JACI, Caubet and colleagues discuss results of their study on the immune responses seen in FPIES due to cow milk (CM-FPIES) (J Allergy Clin Immunol 2017; 139(2): 572-583).

To do this, they looked that the levels of antibodies, cytokines (chemical messengers), cell counts, and tryptase levels in 38 patients with active and resolved CM-FPIES.  Oral food challenges (OFCs) were performed, and the results from positive OFCs were compared to those from negative OFCs.

What they found is that neutrophils could be responsible cells, which were found to be higher in patients with positive oral food challenges.  The high levels of IL-8, a chemoattractant for neutrophils, also supported their conclusion.  Mast cells may also participate, since IL-9 that was also high is produced by mast cells, and baseline tryptase levels were elevated.  But interestingly, tryptase levels didn’t increase with the positive oral food challenge, meaning that mast cells weren’t activated during a challenge.  Regulatory cytokines, such as IL-10 are likely related to the development of oral tolerance in FPIES.  Additionally, levels of antibodies specific to casein, a key component of milk, were low in children with CM-FPIES.    There remain a lot of unanswered questions about FPIES, but this study helps to shine some light on this mysterious type of food allergy.