Linkage of Crohn's disease-related serological phenotypes: NFKB1 haplotypes are associated with anti-CBiri and ASCA, and show reduced NF-κB activation

Academic Article


  • Background and aims: Genetics studies of the serum expression of antibodies to microbial antigens may yield important clues to the pathogenesis of Crohn's disease. Our aim was to conduct a linkage study using expression of anti-CBir1, anti-12, anti-OmpC and ASCA as quantitative traits. Methods: Expression of antibodies to microbial antigens was measured by enzyme-linked immunosorbant assay (ELISA) and a standard ~10 cM whole genome microsatellite study was conducted. Single nucleotide polymorphism genotyping was performed using either Illumina or TaqMan MGB technology. Nuclear factor Kappa B (NF-κB) activation in cells from Epstein-Barr virus (EBV)-transformed cell lines was assessed using an electrophoretic mobility shift assay and protein was measured using ELISA and western blotting. Results: Evidence for linkage to anti-CBir1 expression was detected on human chromosome 4 (logarithm of odds (LOD) 1.82 at 91 cM). We therefore directly proceeded to test the association of haplotypes in NFKB1, a candidate gene. One haplotype, H1, was associated with anti-CBir1 (p = 0.003) and another, H3, was associated with ASCA (p = 0.023). Using cell lines from Crohn's disease patients with either H1 or H3, NF-κB activation and NF-κB p105 and p50 production were significantly lower for patients with H1 compared to patients with H3. Conclusions: These results suggest that NFKB1 haplotypes induce dysregulation of innate immune responses by altering NF-κB expression. The results also show the use of EBV-transformed lymphoblastoid cell lines to conduct phenotypic studies of genetic variation.
  • Published In

  • Gut  Journal
  • Digital Object Identifier (doi)

    Author List

  • Takedatsu H; Taylor KD; Mei L; McGovern DPB; Landers CJ; Gonsky R; Cong Y; Vasiliauskas EA; Ippoliti A; Elson CO
  • Start Page

  • 60
  • End Page

  • 67
  • Volume

  • 58
  • Issue

  • 1