Fecal Human β-Defensin 2 in Children with Cystic Fibrosis: Is There a Diminished Intestinal Innate Immune Response?

Abstract

Background: Defects in bacterial host defenses in the cystic fibrosis (CF) airways have been extensively investigated, but the role of the intestinal innate immune system in CF is unknown. Human β-defensin 2 (HBD-2) is an antimicrobial protein produced by epithelial surfaces and upregulated by inflammation. Its expression in the CF intestine is unknown. Aim: To determine whether HBD-2 was present in the feces of patients with CF, and to compare fecal HBD-2 levels between CF and healthy controls (HC). To compare fecal HBD-2 levels in inflamed and noninflamed states, as measured by fecal calprotectin, as a secondary aim. Methods: Feces from children with CF and HC were collected for analysis. Results: Thirty-three CF patients and 33 HC were recruited. All CF patients had detectable fecal HBD-2. There was no difference between fecal HBD-2 in CF and HC (median (IQR) 49.1 (19.7–77.2) versus 43.4 (26.5–71.9) ng/g; P = 0.7). Fecal calprotectin was significantly higher in the CF cohort than in HC (median (IQR) 61.3 (43.8–143.8) versus 19.5 (19.5–35.1) mg/kg; P < 0.0001). There was no difference in fecal HBD-2 levels between CF subjects with fecal calprotectin ≥50 mg/kg and <50 mg/kg (50.5 (19.6–80.2) versus 43.0 (19.0–70.4); P = 0.7). There was no correlation between fecal HBD-2 and calprotectin in CF (r = 0.14; P = 0.4). Conclusion: Fecal HBD-2 levels were not increased in children with CF, in inflamed or noninflamed states. The lack of HBD-2 induction and upregulation under inflammatory conditions may suggest a diminished intestinal innate immune response in CF.