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.
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Acknowledgments
The authors are highly grateful to all the parents and children participating in the study. We thank Dr. John Morton, Dr. Yvonne Belessis, Dr. Penny Field, Dr. John Widger, Rhonda Bell, Rebecca McDonald, Amanda Thomsen (CF Clinic at Sydney Children’s Hospital Randwick), Lily Nahidi (Sydney Children’s Hospital Clinical Research Centre), Dr. Mark Jacobs, Dr. Kimberley Tan, Dr. Hughie Tsang, Lourdes Lubrin (Eye Clinic at Sydney Children’s Hospital), Roxanne Strachan, and Jung M. Lee.
Grant support
This work was supported by the Cystic Fibrosis Australia Research Trust Grant, the Royal Australasian College of Physicians Research and Education Foundation Award (Servier Staff Research Fellowship), and the Sydney Children’s Hospital Foundation.
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Ooi, C.Y., Pang, T., Leach, S.T. et al. Fecal Human β-Defensin 2 in Children with Cystic Fibrosis: Is There a Diminished Intestinal Innate Immune Response?. Dig Dis Sci 60, 2946–2952 (2015). https://doi.org/10.1007/s10620-015-3842-2
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DOI: https://doi.org/10.1007/s10620-015-3842-2