Assessment of fecal tumor necrosis factor alpha (TNF-α) in infants with non-IgE mediated cow’s milk protein allergy: a case-control study

Abstract Background Non-IgE mediated cow’s milk protein allergy (CMPA) is being increasingly recognized in infants. Tumor necrosis factor alpha (TNF-α) is a cytokine that has been identified as a key modulator of inflammatory responses and is implicated in the pathogenesis of some inflammatory and autoimmune diseases. The influence of immune mechanisms in the pathogenesis of non-IgE mediated CMPA during infancy remains to be clarified. Objectives This study aims to evaluate the role of the gut TNF-α in the susceptibility to non-IgE mediated cow’s milk protein allergy in infants. Methods A case-control study consisted of 88 infants, aged 1–12 months; of these, 60 had challenge-proven non-IgE mediated CMPA appeared as either delayed onset gastrointestinal, skin, and/or respiratory symptoms. Twenty-eight healthy age- and sex-matched infants were studied as controls. TNF-α in the stool of infants was measured by ELISA. Results Gastroesophageal reflux was the most common gastrointestinal symptom (55%) of patients. Cow's Milk related Symptom Score (CoMiSS) was significant between patients and control at p =0.001. The median fecal TNF-α levels were significantly lower in non-IgE mediated CMPA infants compared to control [52 (IQR 11.9-156) pg/mL and 156 (IQR 41-217.7) pg/mL respectively] at p =0.02. At a cutoff threshold of 128 pg/mL, infants with TNF-α levels below this threshold had higher odds of being in the CMPA group ( OR= 2.6; (95% Cl: 1.1-6.6). Conclusions Gastroesophageal reflux is the most common gastrointestinal symptom in non-IgE mediated CMPA. Limited TNF-α production in the gut could contribute to vulnerability to gut inflammation. These results may help to clarify the etiopathology of non-IgE mediated CMPA and explain the rate of tolerance.