title: The CARD8 p.C10X mutation associates with a low anti-glycans antibody response in patients with Crohn's disease.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Université Lille Nord de France, 59000, Lille, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Vasseur
authors.forename: Boualem
authors.initials: B
authors.lastname: Sendid
authors.forename: Franck
authors.initials: F
authors.lastname: Broly
authors.forename: Corinne
authors.initials: C
authors.lastname: Gower-Rousseau
authors.forename: Aurore
authors.initials: A
authors.lastname: Sarazin
authors.forename: Annie
authors.initials: A
authors.lastname: Standaert-Vitse
authors.forename: Jean-Frederic
authors.initials: JF
authors.lastname: Colombel
authors.forename: Daniel
authors.initials: D
authors.lastname: Poulain
authors.forename: Thierry
authors.initials: T
authors.lastname: Jouault
mesh_terms: D000906:Antibodies / Q000235:genetics; D000917:Antibody Formation / Q000235:genetics; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D002686:Chitin / Q000276:immunology; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005936:Glucans / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral / Q000235:genetics*; D058847:Inflammasomes / Q000235:genetics; D008297:Male; D008351:Mannans / Q000276:immunology; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D010375:Pedigree
chemical_list: D000906:Antibodies; D053468:CARD Signaling Adaptor Proteins; C455623:CARD8 protein, human; D005936:Glucans; D058847:Inflammasomes; D008351:Mannans; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D009363:Neoplasm Proteins; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D002686:Chitin