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P160 Need for Recurrent Resection and Complex Phenotype are Associated with a Specific Antibody Signature in Crohn's Disease Patients undergoing Resection. Smoking is Not Associated with Prevalent Antibodies. Prognostic and Mechanistic Implications.

A.L. Hamilton*1, M.A. Kamm2, F. Selvaraj3, F. Princen3, P. De Cruz2, E.K. Wright2, K.J. Ritchie2, E.O. Krejany1, A. Gorelik2, D. Liew2, L. Prideaux2, I.C. Lawrance2, J.M. Andrews2, P.A. Bampton2, M. Sparrow2, T.H. Florin2, P.R. Gibson2, H. Debinski2, R. Gearry2, F.A. Macrae2, R. Leong2, I. Kronborg2, G. Radford-Smith2, W. Selby2, M.J. Johnston2, R. Woods2, P.R. Elliott2, S.J. Bell2, S.J. Brown2, W.R. Connell2, P.V. Desmond2, S. Singh3

1University of Melbourne & St Vincent's Hospital, Department of Medicine, Melbourne, Australia, 2St Vincent's Hospital & University of Melbourne, Department of Gastroenterology, Melbourne, Australia, 3Prometheus Laboratories, Therapeutics & Diagnostics, San Diego, California, United States

Background

Patients with Crohn's disease develop antibodies to microbial antigens as a result of an atypical immune response to the intestinal microbiota. There are limited data on the serologic profile of patients with Crohn's disease who progress to surgery. We assessed the baseline serologic profile of a prospective cohort of patients from the POCER (Post-operative Crohn's Endoscopic Recurrence) Study, prior to surgery for luminal Crohn's disease.

Methods

160 Crohn's disease patients undergoing intestinal resection were prospectively evaluated. Disease phenotype (Montreal Classification), smoking status, surgical history and length of disease history were assessed. Patients were high risk if ≥1 of risk factors for disease recurrence were present (≥1 previous intestinal resection, perforating disease, current smoking). Serological testing was undertaken immediately prior to, or within 4 weeks of, surgery for presence and titre of antibodies: ANCA, pANCA, ASCA IgA/IgG and the bacterial antibodies anti-OmpC, anti-CBir1, anti-A4-Fla2, anti-Fla-X. Positivity and titre magnitude were assessed in relation to phenotype.

Results

160 patients (85% high risk) were assessed. 22 patients (14%) were positive for all and 32 (20%) negative for all bacterial markers (OmpC, CBir1, A4-Fla2, Fla-X). On univariate analysis, positivity for ASCA IgA and anti-OmpC were associated with complex disease (B2/B3) (ASCA: B1 69% v B2/3 93%, P=0.02; anti-OmpC: B1 31% vs B2/3 65%, P=0.018). Current or past smokers were less likely than non smokers to be ASCA IgG positive (27% vs 49%, P= 0.004), anti-OmpC (56% vs 71%, P=0.04) and anti-Fla-X (42% vs 64%, P=0.006). Anti-OmpC was associated with a history of ≥2 previous operation (59% <2 vs 94%; P=0.006). There were no differences between high and low risk patients for any antibodies.

Conclusion

ASCA IgA and anti-OmpC are associated with complex stricturing or fistulising phenotype and anti-OmpC with repeated surgery, suggesting a possible predictive role in managing Crohn's disease. The lower serological antibody prevalence in smokers suggests that smoking exerts its deleterious effect in Crohn's disease through a different mechanism.