title: Cultured blood T-cell responses predict anti-TNF therapy response in patients with ulcerative colitis.
abstract: BACKGROUND
  Anti-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.
  
  
  OBJECTIVE
  To identify prognostic biomarkers of anti-TNF therapy response in anti-TNF therapy-naïve patients with UC.
  
  
  METHODS
  Peripheral 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 12-14 weeks after the first infusion.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  The effects of anti-TNF on cultured blood T cells, obtained before therapy started, predict treatment outcome in patients with UC.
authors: Department of Microbiology and Immunology, Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Internal Medicine and Clinical Nutrition, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: M K
authors: MK
authors: Magnusson
authors: H
authors: H
authors: Strid
authors: S
authors: S
authors: Isaksson
authors: A
authors: A
authors: Bajor
authors: A
authors: A
authors: Lasson
authors: K-A
authors: KA
authors: Ung
authors: L
authors: L
authors: Öhman
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000378:metabolism*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha