Profiles of Lamina Propria T Helper Cell Subsets Discriminate between Ulcerative Colitis and Crohn's Disease

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.