P083 JAK/STAT pathway and IL-6 activity in moderate to severe Ulcerative Colitis

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a high social and health care system burden. Despite recent advances in UC treatment with available drugs acting in different signalling pathways related to the disease, there is still a significant proportion of non-responders who end up being overtreated and exposed to treatment's secondary effects. Therefore, it would be helpful to know the activity of each inflammatory pathway involved in UC pathogenesis in order to tailor the best treatment for each patient. The aim of our study was to measure the activation of JAK/STAT pathway and IL-6 levels in colonic biopsies from patients with UC. Methods A prospective, observational single-centre study was designed and it is currently on going. Adult UC patients with any endoscopic activity (Mayo Endoscopic Score (MES) > 0) in a routine colonoscopy were included. Biopsies from inflamed (endoscopically active) and non-inflamed (endoscopically inactive) colon of each patient were homogenised and processed by using RIPA buffer and ultrasounds to obtain cell lysates. Determination of the activation of JAK/STAT pathway was performed by detecting phosphorylated forms of JAK1, JAK2, JAK3, TYK2, STAT1, STAT3 and STAT4 by Western blot. Human Luminex discovery assay was used for IL-6 quantification. Data are shown as percentage, median, interquartile range (IQR) and mean ± standard deviation as appropriate. Results So far, 19 patients were consecutively included (median age 60.9 years (IQR 40.8-66.6), 58% female). About 47% had left-sided UC, 32% extensive UC and 21% had proctitis. Regarding endoscopic activity, 52.6% of patients showed MES-3, 42.1% MES-2 and 5.2% MES-1. IL-6 was increased in biopsies from inflamed colon, while no IL-6 was found in biopsies from non-inflamed colon (p=0.00). Median IL-6 in inflamed colonic biopsies from patients with MES-2 was 41.5pg/ml (IQR 7.4-106.7) and 51.9pg/ml (IQR 17.5-220.5) in patients with MES-3 (p=0.4) (Figure 1). Every patient showed, at least, one phosphorylated JAK protein and one phosphorylated STAT protein from JAK/STAT pathway in inflamed colonic biopsies. Nevertheless, the pattern of activation of JAK/STAT pathway was different in all patients as shown in Figure 2. Conclusion Different activated forms of JAK and STAT kinases are detected in inflamed colonic biopsies from UC patients, even though the activation pattern of JAK/STAT pathway differs among them. IL-6 levels are increased in inflamed colonic biopsies from UC patients while it is not detected in non-inflamed mucosa.