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* = Presenting author

P757 Genotype-serotype interactions shed light on of the pathophysiology inflammatory bowel diseases

Ben-Shachar S.*1,2, Finezilber Y.3, Elad H.3, Yanai H.2,3, Dotan I.2,3

1Tel Aviv Medical Center affiliated to Tel Aviv university, Genetic Institute, Tel Aviv, Israel 2Tel Aviv University, Department of Medicine, Sackler Faculty of Medicine, Tel Aviv, Israel 3Tel Aviv Medical Center, IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv, Israel

Background

Multiple genetic variants are associated with inflammatory bowel diseases (IBD) but their role in IBD pathophysiology is mostly unclear. Variants in NOD2 and ATG16L1 genes were related to defects in microorganism sensing in IBD. These variants are more prevalent Crohn's disease (CD), but not ulcerative colitis (UC), compared with controls. Serologic responses may reflect loss of tolerance towards luminal microorganisms. The study aim was To evaluate the effect of having variants in NOD2 and ATG16L1 genes on serologic responses in IBD patients

Methods

IBD patients and healthy controls were recruited in a tertiary IBD Center. NOD2 variants (1007fs, G908R, R702W) and the ATG16L1 A300T variant were analyzed in leukocytes DNA using TaqMan chemistry. Anti-glycan-antibodies: Anti- S. cerevisiae antibodies (ASCA), anti-mannobioside carbohydrate antibodies (AMCA), anti-chitobioside carbohydrate antibodies (ACCA) and anti-laminaribioside carbohydrate antibodies (ALCA), were analyzed using Elisa.

Results

Patients [144 CD, 195 UC of whom 126 underwent pouch surgery (pouch group)], and healthy controls (90) were recruited. NOD2 G908 allele was detected in 15% of CD patients compared with up to 4% in the other groups. The ATG16L1 A300T variant was detected in 61% of controls compared with 79–85% in the IBD groups (p<0.05). ASCA levels were elevated in CD compared to all other groups (p<0.01). CD patients with the NOD2 100fs variant had increased ASCA levels compared with CD patients negative for the variant (64% vs. 36% positive ASCA, p<0.01, and 78.0±31.1IU vs. 52.9±50.5IU absolute levels, p<0.05). No increased ASCA levels were detected in CD patients with the missense NOD2 variants compared to those without the variants. Similarly, pouch patients having the NOD2 100fs variant had elevated ASCA levels with 33% of them showing positive ASCA levels compared to 8% in these without this variant (p<0.05). The 100fs variant, detected in two UC patients and six controls, did not affect serologic responses. ACCA levels were highest in CD, and significantly elevated in UC compared to normal controls (p<0.05). Positive ACCA was detected in 26% of CD patients having an ATG16L1 A300T variant (either heterozygote or homozygote state) compared with zero among those without the ATG16L1 A300T variant (p<0.01). Concordantly, ACCA levels were doubled in CD patients with compared to those without the ATG16L1 A300T variant (p<0.05).

Conclusion

Genetic variants impact serologic responses in CD and pouch patients, but not in UC and healthy controls. The difference in genotype- serotype interactions may imply diverse response towards microorganisms in IBD patients with different genetic backgrounds, such as the NOD2 and ATG16L1 functional variants.