Neutrophil-mediated degradation of type III collagen is elevated in inflammatory bowel disease and DSS-induced colitis reflecting early mucosal damage.
Abstract
Inflammatory Bowel Disease (IBD) is characterized by mucosal injury in the gastrointestinal (GI) tract. During an abnormal immune response in the GI tract, excessive secretion of immune-cell proteases occurs. Neutrophils are the first responders, infiltrating into the inflamed interstitial matrix, where type III collagen accumulates. We aimed to develop a biomarker that reflects early inflammation before clinical symptoms arise; allowing us to intervene and prevent cumulative damage. A competitive enzyme-linked immunosorbent assay targeting a human neutrophil elastase degraded neo-epitope fragment of type III collagen (C3-HNE) was developed and assessed in serum samples from DSS-treated rats and a clinical cohort (n = 91, UC and CD). Moreover, C3M, an MMP- mediated type III collagen degradation marker, was tested for comparison. The DSS-treated rats had elevated C3-HNE levels on day 4, while C3M increased on days 10 and 14, compared to the non-DSS treated group. Percentage change analysis showed that C3-HNE rapidly peaked (day 1), while C3M displayed a sustained elevation over time. Serum C3-HNE concentrations increased in patients with IBD, including those in remission, compared to healthy donors, possibly indicating subclinical inflammation. This biomarker may reflect initial mucosal injury and could provide early detection of inflammation for patients in remission, monitoring flare episodes.
