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* = Presenting author

P116 Serologic and genetic markers may predict the development of chronic pouchitis after pouch surgery in ulcerative colitis patients

S. Ben-Shachar*1, 2, Y. Finezilber3, H. Yanai4, 5, H. Elad4, H. Tulchinsky6, 7, I. Dotan4, 5

1Tel Aviv Medical Center, Genetic Institute, Tel Aviv, Israel, 2Tel Aviv university, Department of Pediatrics, Sackler Faculty of Medicine, Tel Aviv, Israel, 3Meir Sapir hospital, Medicine, Kfar Saba , Israel, 4Tel Aviv Medical Center, IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv, Israel, 5Tel Aviv University, Department of Medicine,Sackler Faculty of Medicine, Tel Aviv, Israel, 6Tel Aviv Medical Center, Proctology Unit, Department of Surgery, Tel Aviv, Israel, 7Tel Aviv University, Department of Surgery, Sackler School of Medicine, Tel Aviv, Israel

Background

Serologic markers characterize Crohn's disease (CD) and a minority of ulcerative colitis (UC) patients. NOD2 gene single nucleotide variations (SNVs) and NOD2 InsC mutation were found to be associated with CD but not with UC. UC patients undergoing pouch surgery due to disease complications may develop inflammation in the previously normal small bowel constructing the pouch (pouchitis).The NOD2 InsC mutation is more frequent in UC patients developing pouchitis compared to those with an uninflamed pouch. Several molecular similarities between pouchitis and CD were previously detected. We hypothesized that serologic and genetic similarities characterizing CD will be found in patients with pouchitis.

Methods

Samples from IBD patients and controls were obtained. Pouch patients were defined as having a normal pouch (NP) or chronic pouchitis (CP) according to clinical definitions. Anti-glycan antibodies: anti-Saccharomyces cerevisiae (ASCA) anti-laminaribioside, anti-chitobioside, and anti-mannobioside carbohydrate antibodies (ALCA, ACCA and AMCA, respecitvely), were tested using ELISA. Two single nucleotide variations (SNVs) of missense type in NOD2 gene (R702W/rs2066844, G908R/rs2066845) and the common frameshift alteration (1007FS/rs2066847) were analyzed using polymerase chain reaction.

Results

A total of 144 CD, 69 UC, 111 UC patients after pouch surgery (57 NP, 54 CP), and 90 healthy controls were recruited. Demographic data in pouch and UC patients were comparable except for younger age of UC diagnosis in CP patients (21.7 ± 10.3 vs 30 ± 12.6 years, respectively, p<0.05). All four serologic markers were significantly increased in CD patients compared with controls (P<0.05). In UC ALCA and AMCA levels were elevated compared to controls (P=0.023 and P=0.43, respectively). No significant alteration of serologic markers was detected in NP, however in CP both AMCA and ACCA levels were elevated compared to controls (76 and 62 IU in vs. 44 and 34 IU, respectively). Significant differences in allele frequencies of the three tested NOD2 variants were detected in CD (P<0.05). The NOD2 InsC allele frequencies tended to increase in CP as well: 11.2%, 7.6%, 2.9% and 1.7% in CD, CP,UC and NP, respectively). Interestingly, CD patients with the NOD2 1007FS mutation had significantly increased ASCA levels compared with CD patients without this mutation (77 vs. 52 IU, p=0.01) and a similar pattern was observed for CP.

Conclusion

UC patients developing pouchitis after pouch surgery have specific characteristics. Moreover, CP and CD patients have serologic and genetic similarities. This suggests that the processes causing pouchitis and CD may be similar, and that serologic and genetic markers may predict disease course after pouch surgery