TL1A in the Pathophysiology of Perianal Fistulising Crohn's Disease

ABSTRACT

Perianal fistulas are a disabling complication of Crohn's disease, and current treatment often fails to achieve sustained healing. The underlying pathophysiology is not fully understood, and most previous research has examined established fistula tissue, which may not reflect the processes that precede fistula formation. Therefore, Gudiño et al. studied uninflamed rectal biopsies from patients with Crohn's disease with and without perianal fistulas. In patients with fistulas, the tissue showed increased activity of the signalling molecule TL1A. This molecule activated T cells, which in turn appeared to influence fibroblasts and epithelial cells through a pathway that operates independently of TNF, the target of anti‐TNF therapy. Because TL1A‐targeting drugs are currently under investigation in inflammatory bowel disease, this pathway may offer a treatment option for patients who do not respond to anti‐TNF therapy. However, this was a small cross‐sectional study, including only patients with established fistulas who had all received anti‐TNF treatment, and cannot determine whether the pathway precedes fistula formation.