Colonic lymphoid follicles and NOD2/CARD15 mutational status in Crohn's disease

Abstract

Background: Interactions between the colonic lymphoid system and the genetic background in Crohn's disease are unexplored. This study analysed variations of colonic lymphoid follicles (CLFs) according to the nucleotide-binding oligomerization domain 2 (NOD2) and caspase recruitment domain-containing protein 15 (CARD15) gene in patients with Crohn's disease. Methods: CLFs were characterized by histology and immunohistochemistry in the specimens of 41 patients undergoing colonic resection for Crohn's disease. Variants of the NOD2/CARD15 gene were assessed by denaturing high performance liquid chromatography and confirmed by DNA sequencing. Results: Eleven patients had a heterozygous variant of the NOD2/CARD15 gene. The uninvolved colon of mutants had significantly lower CLF density (0•9 versus 2•7 follicles per cm2; P < 0.001) and proportion of those with a germinal centre (9 versus 22 per cent; P = 0.040) than in non-mutants. In active disease, CLF density increased similarly in patients with and without the mutation. The proportion of extramucosal CLFs was higher in mutants than in non-mutants (34 versus 22 per cent; P = 0.030). No significant difference between groups was recorded for cellular profile and proliferation. Conclusion: Patients with Crohn's disease and the NOD2/CARD15 mutation show a remodelling of CLFs in both uninvolved and actively inflamed intestines. These subjects may have a defective immune response by organized lymphoid structures. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.