Discovery and validation of mucosal TNF expression combined with histological score - a biomarker for personalized treatment in ulcerative colitis

Autor: Terje Løitegård, Jon Florholmen, Jan-Magnus Kvamme, Øystein Kittel Moe, Trine Olsen, Rasmus Goll, Cecilia Vold, Kay-Martin Johnsen, Mona Dixon Gundersen, Petter Tandberg, Gabriele Raschpichler, Knut Johnsen, Sveinung Wergeland Sørbye, Renate Meyer
Rok vydání: 2020
Předmět:
medicine.medical_specialty
Severity of Illness Index
Gastroenterology
03 medical and health sciences
0302 clinical medicine
Internal medicine
antiTNF
Humans
Medicine
Intestinal Mucosa
Precision Medicine
lcsh:RC799-869
Diagnostic odds ratio
Calprotectin
Tumor Necrosis Factor-alpha
business.industry
Reproducibility of Results
VDP::Medisinske Fag: 700::Basale medisinske
odontologiske og veterinærmedisinske fag: 710
General Medicine
Hepatology
medicine.disease
Ulcerative colitis
VDP::Medical disciplines: 700::Basic medical
dental and veterinary science disciplines: 710
Robarts histopathology index
030220 oncology & carcinogenesis
Cohort
Cytokines
Biomarker (medicine)
Colitis
Ulcerative
lcsh:Diseases of the digestive system. Gastroenterology
030211 gastroenterology & hepatology
Histopathology
Tumor necrosis factor alpha
business
Biomarkers
Research Article
Zdroj: BMC Gastroenterology, Vol 20, Iss 1, Pp 1-9 (2020)
BMC Gastroenterology
ISSN: 1471-230X
Popis: 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.
Databáze: OpenAIRE
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