Original Contribution
The American Journal of Gastroenterology (2008) 103, 1197–1202; doi:10.1111/j.1572-0241.2007.01741.x
NOD2/CARD15 Gene Variants Are Linked to Failure of Antibiotic Treatment in Perianal Fistulating Crohn's Disease
Sieglinde Angelberger MD1, Walter Reinisch MD1, Clemens Dejaco MD1, Wolfgang Miehsler MD1, Thomas Waldhoer PhD2, Jan Wehkamp MD3, Cornelia Lichtenberger PhD1, Elke Schaeffeler PhD3, Harald Vogelsang MD1, Matthias Schwab MD3,4 and Alexander Teml MD3
- 1Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, Vienna, Austria
- 2Department of Epidemiology, Institute of Tumour Biology, Medical University Vienna, Vienna, Austria
- 3Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tuebingen, Tuebingen, Germany
- 4Department of Clinical Pharmacology, University of Tuebingen, Tuebingen, Germany
Correspondence: Walter Reinisch, MD, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, A-1090, Währinger Gürtel 18-20, Vienna, Austria.
Received 22 May 2007; Accepted 5 November 2007.
Abstract
OBJECTIVES:
The Crohn's disease (CD) susceptibility gene, nucleotide-binding oligomerizetion domain 2 (NOD2)/caspase recruitment domain 15 (CARD15), is linked to the innate immune response associated with altered epithelial bacterial defense. Its relevance in antibiotic therapy of perianal fistulating CD remains elusive. The aim of the study was to explore systematically the association between NOD2/CARD15 variants and clinical response of perianal fistulas in patients using antibiotic therapy.
METHODS:
Fifty-two patients (median age 36 yr) with draining perianal fistulas were treated with ciprofloxacin (N = 49) or metronidazole (N = 3) for a median duration of 7 wk. Complete response was defined as the absence of any draining fistula despite gentle finger compression. Genotyping for NOD2/CARD15 variants and human beta (
)-defensin 2 (HBD-2) copies was performed by 5' nuclease assays (Applied Biosystems, Foster City, CA). The examiners and laboratory investigators were blinded. The Fisher exact test and Wilcoxon signed rank test were used for statistical analysis.
RESULTS:
Ciprofloxacin was discontinued in one patient due to diarrhea after 2 wk. Complete fistula response was observed in 13 of 39 patients with NOD2/CARD15 wild-type (33.3%) compared with none in patients carrying NOD2/CARD15 variants (0%, P = 0.02). The median number of HBD-2 gene copies between responders and partial/nonresponders was similar.
CONCLUSIONS:
The study result suggests a substantial contribution of NOD2/CARD15 to the antibiotic treatment outcome of perianal fistulating CD. NOD2/CARD15 variants may predispose to an altered intestinal microflora in perianal fistulas that is less responsive to antibiotic treatment.
