Plasminogen activator inhibitor 1 is a novel faecal biomarker for monitoring disease activity and therapeutic response in inflammatory bowel diseases

Jójárt, Boldizsár and Resál, Tamás and Kata, Diána and Molnár, Tünde and Bacsur, Péter and Szabó, Viktória and Varga, Árpád and Szántó, Kata Judit and Pallagi, Petra and Földesi, Imre and Molnár, Tamás and Maléth, József and Farkas, Klaudia (2024) Plasminogen activator inhibitor 1 is a novel faecal biomarker for monitoring disease activity and therapeutic response in inflammatory bowel diseases. JOURNAL OF CROHNS & COLITIS, 18 (3). pp. 392-405. ISSN 1873-9946

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Abstract

Crohn's disease and ulcerative colitis require lifelong treatment and patient monitoring. Current biomarkers have several limitations, therefore, there is an unmet need to identify novel biomarkers in inflammatory bowel disease (IBD). Previously, the role of plasminogen activator inhibitor 1 (PAI-1) was established in the pathogenesis of IBD and suggested as a potential biomarker. Therefore, we aimed to comprehensively analyze the selectivity of PAI-1 in IBD, its correlation with the disease activity, and its potential to predict therapeutic response.Blood, colon biopsy, organoid cultures (OC), and faecal samples were used from active and inactive IBD patients and control subjects. Serpin E1 gene expressions and PAI-1 protein levels and localization in serum, biopsy, and fecal samples were evaluated by qRT-PCR, ELISA, and immunostaining, respectively.The study population comprised 132 IBD patients (56 CD and 76 UC) and 40 non-IBD patients. We demonstrated that the serum, mucosal, and faecal PAI-1 concentration is elevated in IBD patients, showing clinical and endoscopic activity. In responders (decrease of eMayo≥3 in UC; or SES-CD>50% in CD), the initial PAI-1 level decreased significantly upon successful therapy. OCs derived from active IBD patients produced higher concentrations of PAI-1 than the controls, suggesting that epithelial cells could be a source of PAI-1. Moreover, faecal PAI-1 selectively increases in active IBD but not other organic gastrointestinal diseases.The serum, mucosal, and faecal PAI-1 concentration correlates with the disease activity and therapeutic response in IBD, suggesting that PAI-1 could be utilized as a novel non-invasive, disease-specific faecal biomarker in the patient follow-up.

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