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Cultured blood T-cell responses predict anti-TNF therapy response in patients with ulcerative colitis

Artikel i vetenskaplig tidskrift
Författare Maria K Magnusson
Hans Strid
Stefan Isaksson
Antal Bajor
Anders Lasson
Kjell-Arne Ung
Lena Öhman
Publicerad i Alimentary Pharmacology & Therapeutics
Volym 41
Nummer/häfte 11
Sidor 1149-1161
ISSN 0269-2813
Publiceringsår 2015
Publicerad vid Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi
Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition
Sidor 1149-1161
Språk en
Länkar dx.doi.org/10.1111/apt.13192
Ämnesord INFLIXIMAB INHIBITS ACTIVATION, INFLAMMATORY-BOWEL-DISEASE, TERM-FOLLOW-UP, CROHNS-DISEASE, RESCUE THERAPY, ADALIMUMAB, POLYMORPHISMS, ANTIBODIES, INDUCTION, APOPTOSIS, Gastroenterology & Hepatology, Pharmacology & Pharmacy
Ämneskategorier Klinisk medicin, Medicinska grundvetenskaper

Sammanfattning

BackgroundAnti-tumour necrosis factor (TNF) therapy is used for treatment of ulcerative colitis (UC). As approximately 30% of patients with UC do not benefit from the treatment, it is of clinical interest to identify biomarkers of response before therapy is initiated. AimTo identify prognostic biomarkers of anti-TNF therapy response in anti-TNF therapy-naive patients with UC. MethodsPeripheral blood cells were obtained from 56 patients with UC before therapy started. Thirty-four patients were included in an exploratory cohort and 22 patients in a validation cohort. Blood cells were stimulated in vitro with influenza vaccine with and without anti-TNF. T-cell surface receptor expression and cytokine release were determined (in total 17 variables). Treatment response was evaluated using the Mayo score 12-14weeks after the first infusion. ResultsIn the exploratory cohort, blood cells from the patients showed stronger anti-TNF-dependent suppression of T-cell surface receptor expression and cytokine secretion among therapy responders than nonresponders. In particular, anti-TNF suppressed the expression of CD25 on T cells and secretion of interleukin 5, to a higher degree in responders than in nonresponders. These variables were used to a create model to predict therapy outcome, which was confirmed in the validation cohort. Correct classification of future therapy response was achieved in 91% of the cases in the validation cohort. ConclusionThe effects of anti-TNF on cultured blood T cells, obtained before therapy started, predict treatment outcome in patients with UC.

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