title: Profiles of Lamina Propria T Helper Cell Subsets Discriminate Between Ulcerative Colitis and Crohn's Disease.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: *Department of Medicine/Gastroenterology, University of Calgary, Calgary, Alberta, Canada;†Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China;‡Calgary Laboratory Services, Calgary, Alberta, Canada;§Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada; and‖Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Ji
authors.initials: J
authors.lastname: Li
authors.forename: Aito
authors.initials: A
authors.lastname: Ueno
authors.forename: Miriam
authors.initials: M
authors.lastname: Fort Gasia
authors.forename: Joanne
authors.initials: J
authors.lastname: Luider
authors.forename: Tie
authors.initials: T
authors.lastname: Wang
authors.forename: Christina
authors.initials: C
authors.lastname: Hirota
authors.forename: Humberto B
authors.initials: HB
authors.lastname: Jijon
authors.forename: Mailin
authors.initials: M
authors.lastname: Deane
authors.forename: Michael
authors.initials: M
authors.lastname: Tom
authors.forename: Ronald
authors.initials: R
authors.lastname: Chan
authors.forename: Herman W
authors.initials: HW
authors.lastname: Barkema
authors.forename: Paul L
authors.initials: PL
authors.lastname: Beck
authors.forename: Gilaad G
authors.initials: GG
authors.lastname: Kaplan
authors.forename: Remo
authors.initials: R
authors.lastname: Panaccione
authors.forename: Jiaming
authors.initials: J
authors.lastname: Qian
authors.forename: Marietta
authors.initials: M
authors.lastname: Iacucci
authors.forename: Xinyang
authors.initials: X
authors.lastname: Gui
authors.forename: Subrata
authors.initials: S
authors.lastname: Ghosh
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001706:Biopsy; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D003093:Colitis, Ulcerative / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D003424:Crohn Disease / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000378:metabolism; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects; D000069285:Infliximab / Q000627:therapeutic use; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D020825:T-Box Domain Proteins / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D058504:Th17 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D055815:Young Adult; D000098815:T-bet Transcription Factor
chemical_list: D000893:Anti-Inflammatory Agents; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C508017:IL2RA protein, human; D018793:Interleukin-13; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma; D000069285:Infliximab; D000068879:Adalimumab