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

Abstract

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. 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. 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 cm(2); 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. 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.