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


OBJECTIVE
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).


CONCLUSIONS
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.
Discipline of Paediatrics, School of Women's and Children's Health, Medicine, Sydney Children's Hospital, University of New South Wales, High Street, Randwick, Sydney, NSW, 2031, Australia. keith.ooi@unsw.edu.au.|Department of Paediatric Gastroenterology, Sydney Children's Hospital, High Street, Randwick, Sydney, NSW, 2031, Australia. keith.ooi@unsw.edu.au.
Chee Y
CY
Ooi
Discipline of Paediatrics, School of Women's and Children's Health, Medicine, Sydney Children's Hospital, University of New South Wales, High Street, Randwick, Sydney, NSW, 2031, Australia. tamarapangmp@gmail.com.
Tamara
T
Pang
Discipline of Paediatrics, School of Women's and Children's Health, Medicine, Sydney Children's Hospital, University of New South Wales, High Street, Randwick, Sydney, NSW, 2031, Australia. steven.leach@sesiahs.health.nsw.gov.au.
Steven T
ST
Leach
Department of Nutrition and Dietetics, Sydney Children's Hospital, High Street, Randwick, Sydney, NSW, 2031, Australia. Tamarah.Katz@sesiahs.health.nsw.gov.au.
Tamarah
T
Katz
Department of Paediatrics, Christchurch Hospital, University of Otago, Christchurch, 4710, New Zealand. andrew.day@otago.ac.nz.
Andrew S
AS
Day
Discipline of Paediatrics, School of Women's and Children's Health, Medicine, Sydney Children's Hospital, University of New South Wales, High Street, Randwick, Sydney, NSW, 2031, Australia. a.jaffe@unsw.edu.au.|Department of Paediatric Respiratory, Sydney Children's Hospital, High Street, Randwick, Sydney, NSW, 2031, Australia. a.jaffe@unsw.edu.au.
Adam
A
Jaffe
D000293:Adolescent; D015415:Biomarkers / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000276:immunology* / Q000503:physiopathology; D004751:Enteritis / Q000276:immunology* / Q000503:physiopathology; D005243:Feces / Q000737:chemistry*; D005260:Female; D006776:Hospitals, Pediatric; D006801:Humans; D007113:Immunity, Innate; D039841:Leukocyte L1 Antigen Complex / Q000276:immunology / Q000378:metabolism*; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D023083:beta-Defensins / Q000276:immunology / Q000378:metabolism*
D015415:Biomarkers; C106641:DEFB4A protein, human; D039841:Leukocyte L1 Antigen Complex; D023083:beta-Defensins
Biological markers; Cystic fibrosis; Inflammation; Innate immunity