New insights into perianal fistulising CD pathogenesis may lead to new therapeutics

Perianal fistulising Crohn’s disease (PCD) was associated with increased IFN-γ expression and response in fistula tracts and luminal mucosa, probably driven by IFN-γ and T-helper 17 cells. Also, heightened IFN-γ and TNF-α signalling may promote epithelial-mesenchymal transition in PCD.

“PCD has different mucosal cell responses compared with idiopathic perianal fistulas or CD without perianal disease,” explained Dr Siyan Cao (Washington University in St Louis, MO, USA). “And some of these pathogenic pathways may become therapeutic targets for perianal CD.”

The current study collected biopsies from the rectum, fistula tracts, and fistula openings of patients with perianal CD, idiopathic fistulas, and CD without perianal disease. The investigators performed single-cell RNA sequencing to examine the pathogenesis of perianal CD and identify potential therapeutic targets for this disease.

The main findings of the study included that:

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  • perianal CD was associated with enhanced IFN-γ and TNF-α responses in fistula tracts and luminal mucosa of the rectum, colon, and terminal ileum;
  • rectal epithelial cells expressed elevated IFN-γ responsive genes in active perianal CD;
  • increased IFN-γ and TNF-α response may drive epithelial-mesenchymal transitioning in perianal CD;
  • T-helper 17 cells expressed heightened IFN-γ in perianal CD fistulas; and
  • immunohistochemistry showed upregulated IFN-γ and p-STAT1 in perianal CD fistula tracts.

“We are currently working to expand our research and think about testing IFN-γ antagonists in animal models of perianal CD,” Dr Cao concluded.

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   1. Cao S, et al. Pathogenesis and therapeutic targets of perianal fistulizing Crohn’s disease by multi-omics analysis. LB08, UEG Week 2024, 12–15 October, Vienna, Austria.

Medical writing support was provided by Robert van den Heuvel.
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Posted on 17 October 202417 October 2024