ANTI-SACCHAROMYCES CEREVISIAE ANTIBODIES ARE ASSOCIATED WITH DISEASE ACTIVITY AND LOW BODY MASS INDEX, BUT NOT WITH NOD2/CARD15 MUTATIONS IN PEDIATRIC CROHN??S DISEASE

Abstract

Introduction: Crohn's disease (CD) is a polygenic multifactorial heterogeneous disease. Anti-Saccharomyces cerevisiae antibodies (ASCA) are present in 50-80% of CD patients. The reason for the generation of ASCA remains unclear. Recently, some studies have shown that ASCA occur in 25% of healthy family members of patients with CD. Thus, the generation of these antibodies may be genetically determined. Mutations in the NOD2/CARD15 gene are found to be associated with susceptibility to Crohn's disease. So far, there are no reports on the relationship between ASCA and mutations of NOD2/CARD15 gene in the pediatric CD population. Aim: The aim of our study was to investigate the relationship between ASCA, disease phenotype (location of the inflammation, disease activity and body mass index at the time of diagnosis) and NOD2/CARD15 genotype in pediatric Crohn's disease patients. Methods: 38 patients with CD (6-18 years, M/F = 2,3/1) were tested for ASCA (IgA and/or IgG) by enzyme-linked immunosorbent assay. Disease location, body mass index and disease activity at the time of diagnosis were determined. All patients had genotyping performed using sequence specific PCR directed against the wild tipe and the R702W, G908R and 3020insC variants of NOD2/CARD15 gene. Results: 26 of 38 (68,4%) CD patients were ASCA positive (IgG and/or IgA). 12 of 38 (31,6%) CD patients had at least one of the three major mutations of NOD2/CARD15 gene. ASCA positive patients had significantly lower BMI (p = 0,012) and higher pediatric Crohn's disease activity index -PCDAI (p = 0,022) at the time of diagnosis compared to ASCA negative patients. We found a negative association between the presence of ASCA and ileal location of the disease (p = 0,001). There was no association between positive ASCA and the R702W, G908R and 3020insC mutations of NOD2/CARD15 gene (p = 0,926). Summary: In our study ASCA positive patients had significantly lower body mass index and higher disease activity at the time of diagnosis, however, we didn't find the positive correlation between ileal location of the disease and positive ASCA. There was also no association between positive ASCA and the three major mutations of NOD2/CARD15 gene. Conclusion: Although some studies have shown that generation of ASCA may be genetically determined, our study did not confirm the association between the presence of ASCA and the major mutations of NOD2/CARD15 gene in the pediatric CD population. This finding suggests some other genetic factors may be involved in the generation of ASCA.