You are here

Article Text

Article menu
Download PDFPDF
Commentary
NOD2 and pouch complications in UC patients: old-world clinical dogmas give way to biological definitions
  1. Iris Dotan1,
  2. Scott Eric Plevy2
  1. 1IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  2. 2Center for Gastrointestinal Biology and Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
  1. Correspondence to Dr Iris Dotan, Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel; irisd{at}tasmc.health.gov.il

https://doi.org/10.1136/gutjnl-2012-303188

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    The paper by Tyler et al1 describing genetic associations in patients with ulcerative colitis (UC) preoperatively who then develop chronic pouchitis (CP) and a Crohn's disease (CD) like phenotype postoperatively further extend our clinical definitions of CD and UC based on an evolving knowledge of inflammatory bowel disease (IBD) genetics. Many described human IBD susceptibility genes are shared between UC and CD, highlighting overlapping clinical and pathophysiological features. However, single nucleotide polymorphisms (SNPs) in NOD2 (nucleotide-binding oligomerisation domain 2) are the most important genetic risk factors for the occurrence of CD. In individuals of European ancestry, heterozygous carriage of one of the three major risk alleles confers a 2.4-fold increase in risk for CD; homozygous or compound heterozygous carriage confers a 17.1-fold increase in risk for CD.2 ,3 Clinically, NOD2 mutations have been consistently associated with ileal location and stricturing disease.3 ,4 Of the major risk alleles, the insertion mutation NOD2insC which codes for a truncated protein, confers the greatest risk for CD.2

    NOD2 is a member of the NOD-Like Receptor (NLR) (NOD, leucine-rich repeat-containing protein) family of intracellular sensors of microbes and microbial products.5 Progress has been made in understanding NOD2 function in relation to CD pathogenesis. NOD2 has been implicated in the expression of antimicrobial peptides which consequently shape the composition of the enteric microbiota.6 Macrophage and dendritic cell NOD2 regulates the expression of proinflammatory and anti-inflammatory cytokines central to IBD pathogenesis.7 Emerging evidence in mice and humans suggests that NOD2 represents a global regulatory pathway for small bowel inflammation. In mice, loss of Nod2 function alone does not cause intestinal inflammation. However, Nod2-deficient mice express low levels of antimicrobial peptides and reduced capacity to clear enteric microbes.8 Moreover, Nod2-deficient mice in which granulocyte macrophage colony …

    View Full Text

    Footnotes

    • Contributors The two authors contributed equally to the writing of this editorial.

    • Funding ID: partial support from the Leona M and Harry B Helmsley Charitable Trust.

    • Competing interests SEP has been a consultant for Prometheus Laboratories and receives royalties on patents held with Cedars-Sinai Medical Center (Los Angeles, CA) which have been licensed to Prometheus Laboratories.

    • Provenance and peer review Commissioned; externally peer reviewed.

    Linked Articles