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P042 Circulating IL9 in inflammatory bowel disease: possible marker of mucosal non-healing

K. Neubauer*1, M. Krzystek-Korpacka2, M. Matusiewicz2, M. Zawadzki3, I. Bednarz-Misa2, S. Górska4, W. Witkiewicz5, A. Gamian6, 7

1Wroclaw Medical University, Gastroenterology and Hepatology, Wroclaw, Poland, 2Wroclaw Medical University, Medical Biochemistry, Wroclaw, Poland, 3Regional Specialist Hospital, Vascular Surgery, Wroclaw, Poland, 4LudwikHirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Laboratory of Medical Microbiology, Wroclaw, Poland, 5Research and Development Centre at Regional Specialist Hospital, Wroclaw, Poland, 6Medical Wroclaw University, Medical Biochemistry, Wroclaw, Poland, 7LudwikHirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland

Background

The fundamental role of cytokines in the induction of inflammation in inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC) is established. Discovery of Th9 cells, has rekindled an interest in IL9 cytokine. Il9 expression in bowel tissue/leukocytes has been proposed as a marker of inflammation. However, circulating IL9, as a serum-based marker, might prove more easily available indicator of IBD severity. The association between Il9 expression and endoscopic findings is of particular relevance in the light of mucosal healing (MH) becoming a key treatment goal.

Methods

Serum IL9 was measured in 305 individuals: 171 IBD (97 CD; 74 UC), 12 irritable bowel syndrome (IBS), 21 adenomas, 77 colorectal cancer, and 24 apparently healthy controls. Crohn’s Disease Activity Index (CDAI) was applied for the assessment of CD activity and the Mayo Scoring System (MDAI) for UC. Bowel inflammation in UC patients was assessed using Mayo endoscopic score. IL9 was measured in duplicates by means of flow cytometry-based method utilising magnetic microspheres conjugated with monoclonal antibodies using the BioPlex 200 platform with HRF (Bio-Rad, USA), incorporating LuminexxMAP® technology, and Bio-Plex Pro™ Human Cytokine, Chemokine, and Growth Factor Magnetic. The statistical analysis was conducted using MedCalc Statistical Software version 15.8.

Results

Circulating IL9 was significantly lower in healthy individuals than in patients with bowel diseases. Cytokine levels were higher in patients with active compared with inactive CD (27.4 pg/ml (23.4–32.2) vs 15.9 pg/ml (10.8–23.4), p = 0.007) and with active compared with inactive UC (32.4 pg/ml (27–38.8) vs 19.4 pg/ml (13.9–27.1), p = 0.005). There was a weak positive correlation with CDAI (ρ = 0.32, p = 0.003) and MDAI (ρ = 0.35, p = 0.002). Mayo endoscopic sub-score, strongly correlated with IL9 levels (ρ = 0.75, p < 0.0001, n = 50). In logistic regression log-IL9 was an independent predictor of MH (regression coefficient, 16.2, p = 0.001; constant 20.4, p = 0.002; goodness of fit: χ2 = 1.87, p = 0.985), correctly classifying 88% of cases. In ROC analysis, IL9 as a MH marker displayed near perfect accuracy, as well as perfect sensitivity accompanied by high specificity. IL9 performance was expressed as overall accuracy (area under ROC curve, AUC) independent from a threshold selection, as well as sensitivity and specificity at optimal threshold yielding the highest Youden index. IL9 exhibited the strongest association with active IBD. As its marker, IL9 displayed near perfect accuracy, and its sensitivity and specificity were equally high.

Conclusion

Our results demonstrate IL9 elevation in active IBD that might be used for diagnostic purposes, as well as assist in non-invasive evaluation of mucosal healing in IBD.