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* = Presenting author

P230 Elevated angiopoietins independent of TNF α regulation appear to play a key role in immune mediated angiogenesis in inflammatory bowel disease

M. Hussey*1, G. Holleran1, K. Grooteman2, S. Smith3, D. McNamara1

1Adelaide and Meath Hospital, Trinity College Dublin, Gastroenterology, Trinity Academic Gastroenterology Group, Dublin, Ireland, 2Radboud University Medical Centre, Department of Gastroenterology, Nijmegen, Netherlands, 3Trinity College Dublin, Clinical Medicine, Trinity Academic Gastroenterology Group, Dublin, Ireland

Background

Angiogenesis has been proposed to play an important role in the perpetuation of sustained inflammation in IBD. Angiopoietins are critical angiogenic mediators and their potential role as markers of disease activity and therapeutic targets remains unclear. The aim of this study was to measure serum levels of ANG 1 & 2(angiopoeitin 1 & 2) & TNFα (tumour necrosis factor alpha) in IBD patients.

Methods

Following informed consent, IBD patients, aged 18–80 years undergoing a colonoscopy were prospectively recruited. Patient demographics, Harvey–Bradshaw Index and Mayo Score, CRP, and histological and endoscopic grade were recorded. Healthy controls with a normal colonoscopy were also recruited. Serum was collected and stored for batch analysis at -80°C. Commercially available ELISA kits (R&D systems) were used to measure ANG 1, ANG 2, and TNF α levels according to manufacturer’s guidelines. Results were expressed as a mean, and compared between groups, IBD vs controls and active vs inactive disease defined via a CRP (< 5 mg/dl inactive and > 5 mg/dl active).

Results

To date, 31 IBD (15 Crohn’s and 16 UC) and 32 control patients have been recruited. The mean ages were similar (43 vs 47 yr). There were more females amongst the controls, 80% (n = 25) vs 56% (n = 18), (p < 0.04). Amongst IBD patients, overall 9% (n = 3) were in remission; 42% (n = 13) had mild; 26 % (n = 8) moderate; and 23% (n = 7) severe disease endoscopically. Mean HBI was 4 (range 0–7), mean Mayo score 8 (range 0–12) and mean CRP 29 mg/l (range 1–195 mg/dl). Active patients had a mean CRP of 52 mg/dl vs 2.0 mg/l for inactive patients, (p < 0.01, 95% CI 8.907 to 91.130). Overall mean serum levels of Ang-1 were significantly higher in IBD patients vs controls, 46 401.6 vs 41 338.3 pg/ml, (p = 0.05, 95% CI -49.6935–9248.5), whereas ANG2 (2 809.9 vs 2 858.5, p < 0.9) and TNF α levels were similar (7.2 vs 4.7 pg/ml, p < 0.1). Of interest, mean serum ANG-1 levels were significantly higher in patients with biochemically active disease, 50 408.3 vs 40 229.5 pg/ml (p < 0.01, 95% CI 23 43.8–18 013.6). Similarly, within the IBD cohort, mean ANG 2 levels correlated with disease activity, active 3 269 pg/ml vs inactive, 2 148.9 pg/ml (p < 0.02, 95% CI 160.5–2 079.7). Both were independent of TNF α levels, active 6.6 pg/ml vs inactive 7.5 pg/ml (p < 0.8). Of note, there were significantly higher levels of ANG-1 (50 497.7 vs 40 804.7, p < 0.01, 95% CI -1 766.8–1 683.3) and ANG 2 (3 094 vs 2 211.2, p = 0.07) in UC patients; however, this group had significantly more active disease (75% vs 33%, p < 0.02, 95% CI -0.75 to -0.05).

Conclusion

Serum angiopoietin levels are predictive of disease in IBD and may play a role as a non-invasive marker of activity. Identification of novel regulatory cytokines may identify new therapeutic targets and warrant further study.