A functional interleukin-10 mutation in Dutch patients with Crohn's disease

Dig Liver Dis. 2005 May;37(5):330-5. doi: 10.1016/j.dld.2004.12.009.

Abstract

Background and aims: Interleukin-10 is an anti-inflammatory and immunomodulatory cytokine. Interleukin-10 deficient mice are prone to develop chronic colitis. Administration of recombinant human interleukin-10 has been proposed to have a beneficial effect in a subgroup of patients with Crohn's disease. Recently, we found an interleukin-10 Gly15Arg mutation in a family with Crohn's disease which is associated with reduced interleukin-10 secretion by in vitro stimulated monocytes and lymphocytes. We hypothesised that this interleukin-10 mutation plays a role in maintaining the inflammatory process in Crohn's disease in some families.

Patients and methods: We evaluated interleukin-10 Gly15Arg in 379 patients with Crohn's disease, and 75 unrelated healthy controls. Also, first degree family members of interleukin-10 Gly15Arg carriers were evaluated. Additionally, mutation carriers and their relatives were evaluated for CARD15 R702W, G908R, and 1007fs.

Results: Two patients with Crohn's disease were heterozygous for the interleukin-10 Gly15Arg mutation. No homozygotes were found. The Gly15Arg mutation was not observed in the controls. In first degree family members of the Crohn's disease-affected interleukin-10 Gly15Arg carriers, the mutation was found in Crohn's disease-affected as well as in their apparently healthy individuals. All family members carried one or two CARD15 mutation(s).

Conclusion: The interleukin-10 Gly15Arg mutation is rare in patients with Crohn's disease, and is not associated with the disease in the Netherlands.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Arginine / genetics
  • Crohn Disease / genetics*
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease
  • Glycine / genetics
  • Humans
  • Interleukin-10 / genetics*
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Middle Aged
  • Netherlands
  • Nod2 Signaling Adaptor Protein
  • Point Mutation*
  • Restriction Mapping

Substances

  • Intracellular Signaling Peptides and Proteins
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • Interleukin-10
  • Arginine
  • Glycine