P0228Assessment of the diagnostic value of faecal Plasminogen activator inhibitor type 1 (PAI-1) compared to Calprotectin in differentiating Inflammatory Bowel Diseases from other gastrointestinal disorders

Background Inflammatory Bowel Diseases (IBD), including Crohn’s disease (CD) and Ulcerative colitis (UC), require lifelong patient monitoring. Existing predictors of relapse and treatment response are often invasive, costly, and time-consuming. Faecal biomarkers offer a simple, non-invasive alternative for monitoring disease activity. While Faecal Calprotectin (FC) is the current standard, it has several drawbacks. Our previous study indicates that faecal Plasminogen activator inhibitor type 1 (PAI-1) correlates with endoscopic activity and treatment response, suggesting its potential as a novel, stable biomarker for IBD diagnosis. To precisely evaluate faecal biomarker potential, we aimed to determine FP concentrations in patients with IBD and other gastrointestinal diseases and to compare these values with FC concentrations. Methods Faecal samples were collected from 277 patients with IBD (CD-active: 29, CD-inactive: 40, UC-active: 70, UC-inactive: 35) and other GI diseases [colorectal cancer (CRC): 16, diverticulosis [DIV]: 28, irritable bowel syndrome (IBS): 14, adenoma: 23] and 16 healthy subjects. The ELISA method was applied to define the FP level, and it was validated for stool, and 0.53 ng/g PAI-1 level was defined as the cut-off value. For FC observation diagnostic ELISA kit with a recommended 50 mg/g cut-off was applied. ROC, logistic regression, and Confusion matrix analysis were utilized to define the diagnostic potential. Results FP level was significantly higher in patients with active IBD compared to inactive and non-IBD subjects (0.88 vs 0.07 ng/g, p < 0.0001). In addition, FP was significantly increased in active IBD (0.88 ng/g) patients compared to inactive IBD (0.13 ng/g, p < 0.0001), CRC (0.235 ng/g, p = 0.0479), DIV (0.045 ng/g, p < 0.0001), IBS (0.005 ng/g, p < 0.0001), adenoma (0.0 ng/g, p < 0.0001), and healthy (0.0 ng/g, p = 0.0005) subjects. However, FC showed the same pattern as FP, the active IBD was significantly elevated compared to the others. High specificity (84%) and moderate sensitivity (67%) (TP: 70, FP: 27, FN: 34, TN: 146, PPV: 0.72, NPV: 0.81) were defined at the FP measurements. Nevertheless, at FC level, 33% specificity and 97% sensitivity were measured (TP: 101, FP: 116, FN: 3, TN: 57, PPV: 0.47, NPV: 0.95). Calculated Youden index was higher at the FP (0.52) compared to the FC (0.3). On the other hand, the accuracy of the FP is 78% and the FC is 57%. Moreover, the AUC of the FP value was 0.83 and 0.89 at the FC. Conclusion Our findings indicate that FP levels have strong diagnostic value, accurately distinguishing active IBD patients from others and identifying true negatives more precisely than FC. Thus, the FP level could be useful tool in the diagnosis of IBD. Reference: Jójárt B, Resál T, Kata D, Molnár T, Bacsur P, Szabó V, Varga Á, Szántó KJ, Pallagi P, Földesi I, Molnár T, Maléth J, Farkas K. Plasminogen Activator Inhibitor 1 Is a Novel Faecal Biomarker for Monitoring Disease Activity and Therapeutic Response in Inflammatory Bowel Diseases. J Crohns Colitis. 2024 Mar 1;18(3):392-405. doi: 10.1093/ecco-jcc/jjad160. PMID: 37751311; PMCID: PMC10906952. Conflict of interest: Dr. Jójárt, Boldizsár: No conflict of interest Kajári, Lilian: No conflict of interest Resál, Tamás: No conflict of interest Bacsur, Péter: No conflict of interest Kata, Diána: No conflict of interest Farkas, Bernadett: No conflict of interest Ivány, Emese: No conflict of interest Szabó, Viktória: No conflict of interest Földesi, Imre: No conflict of interest Pallagi, Petra: No conflict of interest Molnár, Tamás: Conflict of interest: Tamás Molnár has received speaker’s honoraria from MSD, AbbVie, Egis, Goodwill Pharma, Takeda, Pfizer, Janssen, Sandoz, Phytotec, Roche, Fresenius, Teva, Celltrion, Stada, BMS, Ferring, EwoPharma and SOBI Maléth, József: No conflict of interest Farkas, Klaudia: No conflict of interest