P005. T cell KV1.3 channel expression level in biopsies from patients with active ulcerative colitis is higher in patients treated with immunosuppressants and 5-ASA versus 5-ASA alone
L.K. Hansen1, J. Kjeldsen2, T. Knudsen3, D. Larsen1, R. Köhler1, 1University of Southern Denmark, Institute of Molecular Medicine, Odense, 2Odense University Hospital, Department of Gastroenterology and Hepatology, Odense, 3Hospital of South Denmark, Esbjerg, Department of Gastroenterology and Hepatology, Esbjerg, Denmark
T-cell KV1.3 channels are believed to be important effector proteins during T-cell activation and also in autoimmune disease by controlling T-cell motility, cytokine production, and proliferation. The role of KV1.3 channels in ulcerative colitis (UC) has not been defined yet. Our hypothesis in this study was that KV1.3 has a role in the inflammatory process in active UC.
Biopsies from healthy individuals and patients with relapse of UC during medical treatment were obtained during endoscopic examination. Multiple biopsies were obtained from the inflamed mucosa. Biopsies were analysed with quantitative RT-PCR (qPCR). Expression levels are presented as percentage of GAPDH (reference gene). Patients were divided into subgroups according to their medical treatment with 5-ASA or 5-ASA combined with immunosuppressants (IS: glucocorticoids, azathioprine, and/or infliximab).
We included 8 healthy individuals, 9 UC patients treated with 5-ASA alone, and 7 UC patients treated with 5-ASA+IS.
UC patients treated with 5-ASA+IS had significantly higher expression level of KV1.3 compared to healthy controls (mean 0.90 vs. 0.15; p < 0.05). Furthermore the patients treated with 5-ASA + IS had higher KV1.3 expression level than those treated with 5-ASA alone (mean 0.31; p < 0.05).
Patients with active UC treated with 5-ASA+IS had higher levels of T Cell KV1.3 channels compared to controls and UC patients treated with 5-ASA alone. This suggests that high expression level of KV1.3 either is a consequence of the immunosuppressant therapy itself, disease activity, or an explicit attribute of patients who do not respond well to their treatment. Therefore we speculate that KV1.3 blockers may be beneficial as supplementary treatment for non-responders.