Identification of Gut Biomarkers of FPIES in a Longitudinal Comparative Pediatric Study

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated allergy without known biomarkers. We aimed to compare fecal biomarkers related to gut inflammation and immunity in children with FPIES, with resolved FPIES (tolerant), and in matched controls.

Methods: Stools were collected from FPIES children on elimination diet, before and after an oral food challenge (OFC) performed to assess their natural tolerance, at the end of a follow-up in tolerant FPIES children, and in matched controls (1:1 ratio). Concentrations of calprotectin, EDN (eosinophilic derived neurotoxin), and secretory IgA (sIgA) underwent comparative paired analysis.

Results: Thirty-eight patients were included (age: 1.3 years old, interquartile range: IQR [0.9-2.0]), of which 22 became tolerant during follow-up. Upon inclusion, allergic patients and controls had similar concentrations of calprotectin (38 μg/g [8-85] vs. 27 μg/g [11-46], p = 0.15) and EDN (504 ng/g [275-1252] vs. 516 ng/g [215-844], p = 0.86). However, concentrations of these inflammatory biomarkers increased transiently after a failed OFC (p < 0.001 and p = 0.01 respectively), without correlating with the severity of an allergic reaction. sIgA were higher in allergic than in tolerant patients: 2224 μg/g [878-3529] vs. 794 μg/g [699-1767] (p < 0.01). Calprotectin, EDN, and sIgA were comparable in tolerant patients and controls. sIgA less than 2637 μg/g had a negative predictive value of 75.3% for the differentiation allergic patients from tolerant patients and controls (area under curve: 0.63, 95% CI: 0.52-0.74).

Conclusion: A few days after an acute allergic reaction, there was no detectable chronic gut inflammation in FPIES. sIgA may be a useful tool for clinicians in timing OFC.