P068. High expression level of the T cell potassium channel, KV1.3, is a novel diagnostic marker of inflammatory activity in patients with ulcerative colitis
L.K. Hansen1, T. Knudsen2, J. Kjeldsen3, D. Larsen1, R. Köhler1, 1University of Southern Denmark, Institute of Molecular Medicine, Odense, Denmark, 2Hospital of South Denmark, Esbjerg, Department of Gastroenterology and Hepatology, Esbjerg, Denmark, 3Odense University Hospital, Department of Gastroenterology and Hepatology, Odense, Denmark
T cell KV1.3 and KCa3.1 channels are involved in T cell activation, motility and proliferation. These channels are thought to be expressed in all subsets of T cells. Moreover, KV1.3 is highly expressed in effector memory T cells that are believed to play an important role in autoimmune diseases. Their role in ulcerative colitis (UC) is yet to be explored. Our hypothesis was that the expression level of KV1.3 was associated with disease activity in patients with ulcerative colitis.
Biopsies from healthy individuals (n = 8) and patients (n = 26) with first-time attack or relapse of UC were obtained during endoscopic examination. Multiple biopsies were obtained from the inflamed mucosa. Biopsies were analysed by quantitative RT-PCR (qPCR) and immunohistochemistry. The degree of inflammation was assessed by a gastrointestinal pathologist (scores: 0–3; none, mild, moderate, severe).
mRNA-expression levels of KV1.3 were significantly up-regulated in UC patients with active inflammation compared to controls with no symptoms of inflammatory bowel disease showed (p < 0.01). Expression levels of the other T-cell K+ channel, KCa3.1, were not different between the two groups. KV1.3 protein expression was localized to T-cell infiltrates and macrophages while the colonic mucosa did not express KV1.3. KCa3.1 protein expression was found in the mucosa of both patient groups and also in T-cell and macrophage infiltrates of the UC patients.
The mRNA and protein expression of KV1.3 channels in active UC is strongly associated with the degree of mucosal inflammation. Disease-related increases in KV1.3 might serve therefore as additional diagnostic or prognostic marker for UC. Moreover, the increased expression levels of KV1.3 support the hypothesis that UC could be an autoimmune disease, considering a pathomechanistic involvement of KV1.3-high T cells. Finally, blockers of KV1.3 may be of potential usage as a novel pharmacological treatment option.