TBA (16S160)

Elevated angiopoeitins independent of TNF a regulation appear to play a key role in immune mediated angiogenesis in IBD.

Author(s)

1,2Mary Hussey, 1Grainne Holleran, 1Sinead Smith, 1,2Deirdre McNamara

Department(s)/Institutions

1Trinity Academic Gastroenterology Group

2Department of Gastroenterology, Adelaide and Meath Hospital , Tallaght

Introduction

Angiogenesis has been proposed to play an important role in the perpetuation of sustained inflammation in IBD. Angiopoietins are critical angiogenic mediators & their potential role asmarkers of disease activity & therapeutic targets remains unclear.

Aims/Background

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.

Method

Following informed consent,IBD patients undergoing a colonoscopy were prospectively recruited. Patient demographics,Clinical activity,CRP,histological&endoscopic grade were recorded. Controls with a normal colonoscopy were also recruited.Serum was collected & stored for batch analysis at -80°C.Commercially available ELISA kits were used to measure ANG1,ANG2 & TNFα levels according to manufacturer’s guidelines.Results were expressed as a mean&compared between groups,IBD vs.Controls&Active vs.Inactive disease defined via a CRP (<5mg/dl inactive&>5mg/dl active).

Results

To date 31 IBD(15Crohns&16 UC)&32 control patients have been recruited. The mean ages were similar. There were more females amongst the controls,80% (n=25)vs.56% (n=18),(p<0.04). Amongst IBD patients,9% (n=3) were in remission,42(n=13) had mild,26%(n=8) moderate&23% (n=7)severe disease endoscopically. Mean HBI was 4(range0-7),mean Mayo score 8(range 0-12)& mean CRP 29 mg/l (range 1-195mg/dl). Active patients had a mean CRP of 52mg/l vs. 2.0mg/l for inactive patients,(p<0.01, 95% CI 8.907 to 91.130). Overall mean serum levels of Ang1 were significantly higher in IBD patients vs. controls,46401.6 vs. 41338.3pg/ml,(p=0.05,95% CI -49.6935-9248.5),whilst ANG2 (2809.9 vs. 2858.5, p<0.9)& TNFα levels were similar (7.2 vs. 4.7 pg/ml, p<0.1). Of interest, mean serum ANG1 levels were significantly higher in patients with biochemically active disease, 50408.3vs.40229.5pg/ml (p<0.01,95% CI 2343.8-18013.6). Similarly, within the IBD cohort, mean ANG2 levels correlated with disease activity, active 3269pg/ml vs. inactive, 2148.9 pg/ml (p<0.02,95%CI 160.5-2079.7).Both were independent of TNF α levels, active 6.6pg/ml vs. inactive 7.5 pg/ml (p<0.8). Of note, there were significantly higher levels of ANG1 (50497.7vs.40804.7, p<0.01, 95% CI -1766.8 –1683.3)& ANG2 (3094 vs.2211.2, 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).

Conclusions

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