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Inflamm Bowel Dis ; 22(8): 1779-92, 2016 08.
Article in English | MEDLINE | ID: mdl-27243594

ABSTRACT

BACKGROUND: Distinction between 2 forms of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD), can be challenging. Aberrant mucosal immunity suggests that CD is a T helper type 1 cell (Th1)-driven disease, whereas UC as Th2-driven response. However, whether this paradigm truly distinguishes CD from UC is controversial. We aimed to clarify the discriminating potential of lamina propria Th subsets in patients with IBD. METHODS: Biopsies from 79 patients with IBD and 20 healthy controls were collected for Th subsets analysis (Th1:interferon γ [IFN-γ], T-bet; Th2:interleukin 13 [IL-13], Gata3; Th17:IL-17, RORγt; Treg:FoxP3). The receiver-operating characteristic curves were constructed to assess the discriminating ability by calculating the area under the receiver-operating characteristic curve. The equation with the highest area under the receiver-operating characteristic curve was applied to newly diagnosed patients to evaluate discriminating ability. RESULTS: Patients with CD showed increased IFN-γ or T-bet cells and decreased IL-13 or Gata3 cells compared with UC. A discriminant equation composed of 4 markers (IFN-γ, T-bet, IL-13, and Gata3) yielded the highest area under the receiver-operating characteristic curve. In 36 established CD or UC, the sensitivity, specificity, positive and negative predictive probabilities were 92.6%, 55.6%, 86.2%, and 71.4% and in 14 newly diagnosed patients were 100.0%, 42.9%, 63.6%, and 100.0%. Furthermore, Gata3 cells were increased in tumor necrosis factor inhibitor therapy nonresponders compared with responders in CD. IFN-γ cells were directly and inversely proportional to disease activity in patients with CD and UC, respectively. CONCLUSIONS: The Th1/Th2 paradigm can distinguish CD from UC and may be further associated with response to tumor necrosis factor inhibitor in CD and disease activity in patients with IBD.


Subject(s)
CD4-Positive T-Lymphocytes/pathology , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/immunology , Crohn Disease/diagnosis , Crohn Disease/immunology , Intestinal Mucosa/immunology , T-Lymphocyte Subsets/pathology , Adalimumab/therapeutic use , Adolescent , Adult , Aged , Anti-Inflammatory Agents/therapeutic use , Biopsy , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/metabolism , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/pathology , Crohn Disease/drug therapy , Crohn Disease/pathology , Female , Flow Cytometry , Forkhead Transcription Factors/metabolism , GATA3 Transcription Factor/metabolism , Humans , Immunity, Mucosal/drug effects , Infliximab/therapeutic use , Interferon-gamma/metabolism , Interleukin-13/metabolism , Interleukin-17/metabolism , Interleukin-2 Receptor alpha Subunit/metabolism , Intestinal Mucosa/pathology , Male , Middle Aged , Predictive Value of Tests , Severity of Illness Index , T-Box Domain Proteins/metabolism , T-Lymphocyte Subsets/drug effects , T-Lymphocyte Subsets/metabolism , T-Lymphocytes, Regulatory/metabolism , Th1 Cells/metabolism , Th17 Cells/metabolism , Th2 Cells/metabolism , Young Adult
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