Circulating Extracellular Matrix Products as Indicators of Disease Burden and Predictors of Disease Course in Ulcerative Colitis

• Published in: Inflammatory bowel diseases
• Main Authors: Poulsen, Anja, Alexdóttir, Marta Sorokina, Riis, Lene Buhl, Pehrsson, Martin, Sørensen, Lars Tue, Krarup, Peter-Martin, Bay-Jensen, Anne-Christine, Karsdal, Morten A, Stidham, Ryan W, Burisch, Johan, Mortensen, Joachim Høg, Seidelin, Jakob Benedict
• Format: Journal Article
• Language: English
• Published: England 22-10-2024
• Subjects: biomarkers; ulcerative colitis; ECM
• ISSN: 1078-0998; 1536-4844; 1536-4844
• DOI: 10.1093/ibd/izae244

Ulcerative colitis (UC) is characterized by recurrent inflammation and challenging disease monitoring, with invasive endoscopy as the primary diagnostic tool despite the inadequacy of standard noninvasive biomarkers. This study evaluates serum extracellular matrix (ECM) fragments, which reflect the remodeling of mucosa and submucosa, as potential indicators of disease burden and treatment efficacy. We aim to determine whether serum ECM levels correlate with the extent and severity and predict treatment response.
We conducted a prospective study comparing serum ECM formation (PRO-C3, PRO-C7, PRO-C11, PRO-C22), turnover (PRO-C4), and degradation markers (C1M, C3M, C4M, C7M) at Weeks 0, 12, and 24 in 49 UC patients and 50 healthy controls measured by enzyme-linked immunosorbent assay.
ECM biomarkers, notably PRO-C11, differentiated UC patients from controls (area under the curve [AUC] 0.77), and PRO-C3 predicted endoscopic treatment response vs nonresponse (AUC 0.74). C7M separated moderate from severe disease in endoscopy (AUC 0.74) as well as mild from severe disease (AUC 0.84), as did the ratio C7M/PRO-C7 (AUC 0.82). Combining new and conventional markers, including hemoglobin, C-reactive protein, PRO-C3, and PRO-C22, achieved a combined AUC of 0.84 for predicting 24-week endoscopic response, adding index endoscopic activity increased the AUC to 0.92 compared to an AUC of 0.84 for endoscopy alone.
Soluble ECM fragments reflect endoscopic disease severity and extent and are also predictive of therapeutic efficacy. They may as well reflect degenerative aspects of UC and may as such be future therapeutic targets aimed at prevention of intestinal damage.