Association Between Ex Vivo Human Ulcerative Colitis Explant Protein Secretion Profiles and Disease Behaviour.

Area of Science:

• Gastroenterology
• Immunology
• Biomarker Discovery

Background:

• Ulcerative colitis (UC) exhibits variable clinical courses, highlighting an unmet need for biomarkers predicting disease behavior.
• Current diagnostic and prognostic tools for UC require enhancement for personalized treatment strategies.

Purpose of the Study:

• To investigate the association between protein secretion profiles from ex vivo human UC explant-conditioned media (explant-CM) and UC disease behavior.
• To identify potential biomarkers for predicting UC disease progression and anti-tumor necrosis factor (anti-TNF) therapy response.

Main Methods:

• Prospective recruitment of UC patients undergoing endoscopy.
• Generation of explant-CM from endoscopic biopsies.
• Analysis of explant-CM protein profiles and correlation with disease progression (defined by treatment escalation, hospitalization, or surgery) and anti-TNF failure.

Main Results:

• Reduced interleukin-2 (IL-2) secretion was independently associated with UC disease progression (p=0.01).
• Increased IL-17A/F and IL-12/IL-23p40 concentrations correlated with anti-TNF failure (p=0.015 and p=0.044, respectively).
• FLT-1 secretion was independently associated with anti-TNF failure (p=0.016).

Conclusions:

• Decreased IL-2 secretion in explant-CM is a potential biomarker for UC disease progression.
• Ex vivo UC explants represent a promising tool for precision medicine in inflammatory bowel disease.
• Further research into IL-23 pathway cytokines and FLT-1 may refine anti-TNF therapy selection.