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P459 Change in the expression of SerpinE1, a potential new disease activity marker, reflects therapeutic response in Inflammatory Bowel Disease

Jójárt, B.(1);Molnár, T.(2);Szabó, V.(1);Varga, Á.(1);Resál, T.(3);Szántó, K.(3);Kata, D.(4);Földesi, I.(4);Molnár, T.(3);Maléth, J.(5);Farkas, K.(3);

(1)University of Szeged, Faculty of Medicine- First Department of Medicine- HAS-USz Momentum Epithelial Cell Signaling and Secretion Research Group- HCEMM-USz Molecular Gastroenterology Research Group, Szeged, Hungary;(2)University of Szeged, Faculty of Medicine- First Department of Medicine- HAS-USz Momentum Epithelial Cell Signaling and Secretion Research Group, Szeged, Hungary;(3)University of Szeged, Faculty of Medicine- First Department of Medicine, Szeged, Hungary;(4)University of Szeged, Faculty of Medicine - Institute of Laboratory Medicine, Szeged, Hungary;(5)University of Szeged, Faculty of Medicine- First Department of Medicine- Department of Public Health- HAS-USz Momentum Epithelial Cell Signaling and Secretion Research Group- HCEMM-USz Molecular Gastroenterology Research Group, Szeged, Hungary; Hungarian Academy of Science - University of Szeged Momentum Epithelial Cell Signaling and Secretion Research Group

Background

Inflammatory Bowel Disease (IBD) occurs as a consequence of abnormal immune response generating unbalance between pro- and anti-inflammatory signalling. Analysis of cytokine profiles in view of different cytokine targeting or immunosuppressive therapy may open up new therapeutic targets and may reveal biological profiles that distinguish responders from non-responders before initiating therapy.
The aim of present study was to determine cytokine profile of IBD patients and identify cytokines with predictive potential.

Methods

IBD patients with clinically active disease were enrolled in study. Blood and biopsy samples were obtained from 22 IBD patients and 5 healthy controls. Biopsies were taken from inflamed and non-inflamed part of colon of IBD patients. Total protein and mRNA were isolated from biopsy samples. Cytokine Array was used to analyse cytokine expression patterns. Serum and mucosal SerpinE1 levels were measured by ELISA and qRT-PCR.

Results

In samples from IBD patients, remarkable discrimination between inflamed, or non-inflamed areas was observed, whereas no pro-inflammatory cytokines were detected in control samples. SerpinE1 was presented in every inflamed biopsy samples, which was analyzed in more details. Mucosal expression of SerpinE1 differed significantly in healthy subjects compared to IBD patients with active disease (0 vs 24.06 pg/mg, p=0.02). After therapy induction a remarkable decrease was observed in the mucosal SerpinE1 concentration in responders (45.5 vs 9.7 pg/mg, p=0.02) versus non-responders (45 vs 61.2 pg/mg, p=0.3). Moreover, mean value of mucosal SerpinE1 did not differ significantly in healthy subjects compared to responders (5.7 vs. 0 pg/mg, p=0.12). In non-responders the fold changes of SerpinE1 gene expressions were significantly (p=0.001) higher than in responders. Lowest expression of SerpinE1 gene was measured in control samples, whereas the highest in untreated, inflamed biopsy samples. Serum and mucosal SerpinE1 concentrations were significantly higher in patients with active disease compared to inactive (tissue: 5 vs 47.4 pg/mg, p=0.00003; serum: 22.4 vs 25.94 mg/ml, p=0.022). Correlation analysis revealed that serum SerpinE1 correlates with disease activity (p<0,01, cut-off value: 22 mg/ml, sensitivity=80%, specificity=60%, accuracy=74%), whereas no correlation was observed between the mucosal SerpineE1 concentration and the disease activity (p>0.1, sensitivity=72%, specificity=77.8%, accuracy=73.5%).

Conclusion

These results suggest that serum and mucosal SeprinE1 expression reflects endoscopic activity of IBD. Correlation of SerpinE1expression between the blood and the bowel mucosa would open up new possibilities in non-invasive disease monitoring of IBD.

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