The CARD8 p.C10X mutation associates with a low anti-glycans antibody response in patients with Crohn's disease

Francis Vasseur, Boualem Sendid, Franck Broly, Corinne Gower-Rousseau, Aurore Sarazin, Annie Standaert-Vitse, Jean Frederic Colombel, Daniel Poulain, Thierry Jouault

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background: Crohn's disease (CD) is associated with elevated anti-glycans antibody response in 60% of CD patients, and 25% of healthy first-degree relatives (HFDRs), suggesting a genetic influence for this humoral response. In mice, anti-glucan antibody response depends on the NLRP3 inflammasome. Here, we explored the effect of mutated CARD8, a component of the inflammasome, on anti-glycans antibody response in human.Methods: The association between p.C10X mutation (rs2043211) of the CARD8 gene and the levels of anti-glycans antibody response was examined in 39 CD families. The family-based QTDT association test was used to test for the genetic association between CARD8 p.C10X mutation and anti-glycan antibodies in the pedigrees. The difference in antibody responses determined by ELISA was tested in a subgroup of CD probands (one per family) and in a subgroup of HFDRs using the Wilcoxon Kruskal Wallis non-parametric test.Results: The QTDT familial transmission tests showed that the p.C10X mutation of CARD8 was significantly associated with lower levels of antibody to mannans and glucans but not chitin (p=0.024, p=0.0028 and p=0.577, for ASCA, ALCA and ACCA, respectively). These associations were independent of NOD2 and NOD1 genetic backgrounds. The p.C10X mutation significantly associated or displayed a trend toward lower ASCA and ALCA levels (p=0.038 and p=0.08, respectively) only in the subgroup of CD probands. Such associations were not significant for ACCA levels in both subgroups of CD probands and of HFDRs.Conclusion: Our results show that ASCA and ALCA but not ACCA levels are under the influence of CARD8 genotype. Alteration of CARD8, a component of inflammasome, is associated with lower levels of antibodies directed to mannans and glucans at least in CD patients.

Original languageEnglish
Article number35
JournalBMC Medical Genetics
Volume14
Issue number1
DOIs
StatePublished - 18 Mar 2013
Externally publishedYes

Keywords

  • ASCA/ALCA
  • Adaptive immunity
  • Anti-glycan antibodies
  • CARD8/TUCAN
  • Crohn's disease
  • Inflammasome

Fingerprint

Dive into the research topics of 'The CARD8 p.C10X mutation associates with a low anti-glycans antibody response in patients with Crohn's disease'. Together they form a unique fingerprint.

Cite this