Introduction
Inflammatory Bowel Diseases (IBD) require lifelong treatment and patient monitoring. Current predictors of relapse and therapeutic success have limitations, mostly invasive, time-consuming, and expensive. The faecal biomarker can help to monitor the disease activity and therapeutic response by simple and non-invasively. Faecal Calprotectin (FC) is the gold-standard, but it has many disadvantages. We previously described that the correlation between the faecal Plasminogen activator inhibitor type 1 (PAI-1) (FP) level and the endoscopic activity and therapeutic response promote that it could be used as a novel non-invasive faecal biomarker in IBD diagnosis. Moreover, the faecal PAI-1 protein level is stable at room temperature and 4°C.
Aims & Methods
To observe the exact faecal biomarker potential, we aimed to define the FP level of IBD patients and subjects with other gastrointestinal (GI) diseases and compare it with the FC. Faecal samples were collected from 128 patients with IBD (CD-active: 18, CD-inactive: 10, UC-active: 20, UC-inactive: 10) and other GI diseases [colorectal cancer (CRC): 20, diverticulosis [DIV]: 21, irritable bowel syndrome [IBS]: 10, adenoma: 10) and 9 healthy subjects. ELISA method was applied to define FP level, and it was validated for stool samples by us and 0.5 ng/g PAI-1 level was defined as the cut-off value. For FC observation diagnostic FC ELISA kit (Orgentec) was used. 50 mg/g cut-off value was applied at FC. Confusion matrix analysis was utilized to define Youden-index, positive predictive value (PPV), negative predictive value (NPV), accuracy, specificity, and sensitivity of the measured values.
Results
FP level was significantly higher in patients with active IBD compared to inactive and non-IBD subjects (0.64 vs 0.0 ng/g, p<0.0001). No significant differences were observed between CD-active and UC-active groups (0.46 vs 0.79 ng/g, p=0.65). In addition, FP concentrations were significantly increased in active IBD (0.76 pg/g) patients compared to inactive IBD (0.0 pg/g, p=0.0001), CRC (0.11 ng/g, p=0.02), DIV (0.05 ng/g, p=0.001), IBS (0.0 ng/g, p<0.0001), adenoma (0.0 ng/g, p<0.0001), and healthy (0.0 ng/g, p=0.0002) subjects. However, FC showed the same pattern as FP, except at the CRC, adenoma and DIV. In these groups, there were no significant differences compared to the active IBD (487.4 mg/g) subjects (vs CRC: 147.1 mg/g, p=0.09; p=; adenoma: 159.8, p=0.056. Confusion matrix analysis defined high specificity (83.5%) and moderate sensitivity (57.9%) values (TP: 22, FP: 14, FN: 17, TN: 71, PPV: 0.61, NPV: 0.816) at the FP measurements. Nevertheless, at FC levels 35.3% specificity and 94.7% sensitivity were measured (TP: 36, FP: 55, FN: 2, TN: 30, PPV: 0.396, NPV: 0.938). Calculated Youden-index was higher at the FP (0.41) compared to the FC (0.3). On the other hand, the accuracy of the FP is 75.6% and the FC is 53.6%. Based on the results of all FP levels measured (N=299) so far, the calculated values were specificity: 78%, sensitivity: 62%, PPV: 0.63, NPV: 0.78, Youden-index: 0.4, accuracy: 72.3%.
Conclusion
Our results suggest that the FP level selectively increased in the active IBD and discriminated more specifically from the other GI diseases compared to the FC. However, the sensitivity was lower, but it was improved by the increasing patient numbers at the pooled FP levels. Thus, the FP level could be useful in the diagnosis of IBD independently or combined with FC.
References
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.
