Subclinical Intestinal Inflammation in Siblings of Children with Crohn's Disease

Intestinal permeability and altered inflammatory responses, along with genetic and environmental factors, likely contribute to the pathogenesis of Crohn's disease. This study aimed to assess the presence and prevalence of subclinical intestinal inflammation among apparently healthy, first-degree relatives of pediatric patients with Crohn's disease, using non-invasive fecal markers. Stool samples were collected from 13 patients with Crohn's disease, 36 siblings and 41 parents. S100A12 levels were measured using an in-house ELISA assay and calprotectin levels were determined using the PhiCal test, with levels compared to normal healthy population controls. Fecal S100A12 levels in siblings (median, 14 mg/kg; 95% confidence interval [CI], 9-32 mg/kg) and patients (71 mg/kg; CI 4-286 mg/kg) differed significantly from pediatric controls (1 mg/kg; CI 1-5 mg/kg; p < 0.001). In contrast, fecal calprotectin levels in siblings (22 mg/kg; CI 15-31 mg/kg) were lower than that of pediatric controls (31 mg/kg; CI 19-52 mg/kg; p = 0.03). Fecal markers were not elevated in parents compared to adult controls. This study provides further evidence of subclinical intestinal inflammation amongst first-degree relatives of patients with Crohn's disease. The presence of sub-clinical gut inflammation may be a risk factor for the subsequent development of Crohn's disease.