Email updates

Keep up to date with the latest news and content from BMC Medical Genetics and BioMed Central.

Open Access Research article

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

Francis Vasseur12459, Boualem Sendid12379, Franck Broly1289, Corinne Gower-Rousseau459, Aurore Sarazin123, Annie Standaert-Vitse1279, Jean-Frederic Colombel12369, Daniel Poulain12379 and Thierry Jouault12379*

Author Affiliations

1 Université Lille Nord de France, Lille, 59000, France

2 UDSL, Lille, 59000, France

3 Inserm U995, Team 2, Faculté de Médecine H. Warembourg, Pôle Recherche, Place Verdun, Lille, F-59000, France

4 EA2694, Lille, 59000, France

5 Pôle de Santé Publique, Lille, 59000, France

6 Service des Maladies de l’Appareil Digestif et de la Nutrition, Lille, 59000, France

7 Service de Parasitologie Mycologie, Institut de Microbiologie, Lille, 59000, France

8 EA2679, Lille, 59000, France

9 CHRU Lille, Lille, 59000, France

For all author emails, please log on.

BMC Medical Genetics 2013, 14:35  doi:10.1186/1471-2350-14-35

Published: 18 March 2013

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.

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