Association between ASCA-positivity and carrier of a CARD-15 mutation in patients with Crohn's disease

Objective

We investigated whether there is a link between two markers for Crohn's disease (CD): the CD susceptibility mutations in the CARD15 gene and the serologic anti-Saccharomyces cerevisiae (ASCA) antibodies. Both markers may, in some way, also be associated with spondyloarthropathy (SpA), which is known to be related to inflammatory bowel disease.

Methods

Serum samples of 109 CD patients were analysed for IgA and IgG ASCA with a commercial ELISA kit. A RFLP-PCR technique was used to genotype all patients for three single-nucleotide polymorphisms (SNPs) in the CARD15 gene: R702W, G908R and 1007 fs. Every SNP was verified by direct sequencing.

Results

The overall carrier frequency of a CARD15 mutation in CD was 50.5%. ASCA-positivity for IgA, IgG and IgG or IgA was found in respectively 31.2%, 31.2% and 43.1%.

Chi-square testing showed a positive association between CARD15 mutation and ASCA IgA (P = 0.001, OR = 4.167, CI 1.709–10.157), IgG (P = 0.005, OR = 3.406, CI 1.428–8.124) and IgA or IgG (P = 0.005, OR = 3.068, CI 1.391–6.764).

Conclusion

CARD15 mutations and ASCA are not independent risk factors for CD. Instead, they are significantly associated with each other in a population of CD patients (both for ASCA IgA and IgG isotype). This could be interpreted in a double way. CARD15 mutations and ASCA may be both associated with a particular, as-yet-undefined, phenotypic subset of CD. Or CARD15, as an immune-response gene, may in some way modulate humoral immunity, predisposing to the generating of ASCA.