Discovery and validation of mucosal TNF expression combined with histological score - a biomarker for personalized treat
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RESEARCH ARTICLE
Open Access
Discovery and validation of mucosal TNF expression combined with histological score - a biomarker for personalized treatment in ulcerative colitis Jon R. Florholmen1,2,3, Kay-Martin Johnsen1,2* , Renate Meyer1, Trine Olsen1,2, Øystein K. Moe1,4, Petter Tandberg3, Mona D. Gundersen1,2, Jan-Magnus Kvamme1,2, Knut Johnsen1,4, Terje Løitegård5, Gabriele Raschpichler6, Cecilia Vold7, Sveinung W. Sørbye8 and Rasmus Goll1,2
Abstract Background: There are no accurate markers that can predict clinical outcome in ulcerative colitis at time of diagnosis. The aim of this study was to explore a comprehensive data set to identify and validate predictors of clinical outcome in the first year following diagnosis. Methods: Treatment naive-patients with ulcerative colitis were included at time of initial diagnosis from 2004 to 2014, followed by a validation study from 2014 to 2018. Patients were treated according to clinical guidelines following a standard step-up regime. Patients were categorized according to the treatment level necessary to achieve clinical remission: mild, moderate and severe. The biopsies were assessed by Robarts histopathology index (RHI) and TNF gene transcripts. Results: We included 66 patients in the calibration cohort and 89 patients in the validation. Mucosal TNF transcripts showed high test reliability for predicting severe outcome in UC. When combined with histological activity (RHI) scores the test improved its diagnostic reliability. Based on the cut-off values of mucosal TNF and RHI scores from the calibration cohort, the combined test had still high reliability in the validation cohort (specificity 0.99, sensitivity 0.44, PPV 0.89, NPV 0.87) and a diagnostic odds-ratio (DOR) of 54. Conclusions: The combined test using TNF transcript and histological score at debut of UC can predict severe outcome and the need for anti-TNF therapy with a high level of precision. These validated data may be of great clinical utility and contribute to a personalized medical approach with the possibility of top-down treatment for selected patients. Keywords: antiTNF, Calprotectin, Cytokines, Diagnostic odds ratio, Robarts histopathology index
* Correspondence: [email protected] 1 Research Group of Gastroenterology and Nutrition, Department of Clinical Medicine, University of Tromsø, Tromsø, Norway 2 Department of Gastroenterology, Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indica
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