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

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Ji Li1, Aito Ueno, Miriam Fort Gasia

  • 1*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.

Inflammatory Bowel Diseases
|June 1, 2016
PubMed

Insights

The T helper 1 (Th1)/T helper 2 (Th2) paradigm effectively distinguishes Crohn's disease (CD) from ulcerative colitis (UC) using specific immune cell markers. This classification also correlates with treatment response and disease activity in inflammatory bowel disease (IBD).

Area of Science:

  • Immunology
  • Gastroenterology
  • Molecular Biology

Background:

  • Differentiating between ulcerative colitis (UC) and Crohn's disease (CD), two forms of inflammatory bowel disease (IBD), is clinically challenging.
  • Existing theories propose CD is T helper type 1 (Th1)-driven and UC is T helper type 2 (Th2)-driven, but this paradigm requires validation.
  • Investigating lamina propria T helper cell subsets is crucial for understanding IBD pathogenesis and distinguishing between CD and UC.

Purpose of the Study:

  • To evaluate the potential of lamina propria T helper cell subsets in distinguishing between Crohn's disease (CD) and ulcerative colitis (UC).
  • To assess the correlation between T helper cell profiles and response to tumor necrosis factor inhibitor therapy in CD.
  • To examine the relationship between T helper cell subsets and disease activity in patients with IBD.

Main Methods:

  • Analysis of T helper cell subsets (Th1, Th2, Th17, Treg) using specific markers (interferon-γ, T-bet, interleukin-13, Gata3, IL-17, RORγt, FoxP3) in biopsies from 79 IBD patients and 20 controls.
  • Utilization of receiver-operating characteristic (ROC) curves to determine the diagnostic accuracy of different marker combinations.
  • Application of a derived discriminant equation to newly diagnosed IBD patients to validate its discriminating ability.

Main Results:

  • Crohn's disease (CD) patients exhibited higher frequencies of Th1 cells (IFN-γ, T-bet) and lower frequencies of Th2 cells (IL-13, Gata3) compared to ulcerative colitis (UC) patients.
  • A discriminant equation incorporating IFN-γ, T-bet, IL-13, and Gata3 demonstrated high diagnostic accuracy (AUC) for differentiating CD from UC.
  • Gata3 cell levels were elevated in non-responders to tumor necrosis factor inhibitor therapy in CD, while IFN-γ levels correlated with disease activity in CD and UC.

Conclusions:

  • The T helper 1 (Th1)/T helper 2 (Th2) immune response paradigm is a valid method for distinguishing between Crohn's disease (CD) and ulcerative colitis (UC).
  • This Th1/Th2 classification is associated with therapeutic response to tumor necrosis factor inhibitors in CD patients.
  • The Th1/Th2 balance also correlates with disease activity across different inflammatory bowel diseases (IBD).
Abstract

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