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

ABSTRACT 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.