Elevated ectodomain of type 23 collagen is a novel biomarker of the intestinal epithelium to monitor disease activity in ulcerative colitis and Crohn's disease

Abstract

Background Impaired intestinal epithelial barrier is highly affected in inflammatory bowel disease. Transmembrane collagens connecting the epithelial cells to the extracellular matrix have an important role in epithelial cell homeostasis. Thus, we sought to determine whether the transmembrane type 23 collagen could serve as a surrogate marker for disease activity in patients with Crohn’s disease and ulcerative colitis. Methods We developed an enzyme-linked immunosorbent assay to detect the ectodomain of type 23 collagen (PRO-C23) in serum, followed by evaluation of its levels in both acute and chronic dextran sulfate sodium colitis models in rats and human inflammatory bowel disease cohorts. Serum from 44 Crohn’s disease and 29 ulcerative colitis patients with active and inactive disease was included. Results In the acute and chronic dextran sulfate sodium-induced rat colitis model, the PRO-C23 serum levels were significantly increased after colitis and returned to normal levels after disease remission. Serum levels of PRO-C23 were elevated in Crohn’s disease ( p < 0.05) and ulcerative colitis ( p < 0.001) patients with active disease compared to healthy donors. PRO-C23 differentiated healthy donors from ulcerative colitis (area under the curve: 0.81, p = 0.0009) and Crohn’s disease (area under the curve: 0.70, p = 0.0124). PRO-C23 differentiated ulcerative colitis patients with active disease from those in remission (Area under the curve: 0.75, p = 0.0219) and Crohn’s disease patients with active disease from those in remission (area under the curve: 0.68, p = 0.05). Conclusion PRO-C23 was elevated in rats with active colitis, and inflammatory bowel disease patients with active disease. Therefore, PRO-C23 may be used as a surrogate marker for monitoring disease activity in ulcerative colitis and Crohn’s disease.

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“…A new enzyme-linked immunosorbent assay test was developed ad hoc for this investigation. 17 Lastly, using cultured mucosal biopsies from inflammed and uninflammed areas of IBD patients, the manipulation of the cannabinoid system seemed to affect colon cells and secretome characteristics that might facilitate mucosal healing, giving new insights on possible future therapeutic measures. 18…”

“…Moving to IBD translational studies, the cleaved form of the cell adhesion regulator type 23 collagen (PRO‐C23) was found to be a potential biomarker to monitor disease activity in IBD, as shown elevated in mouse models and human serum of patients. A new enzyme‐linked immunosorbent assay test was developed ad hoc for this investigation 17 …”

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“…We have been privileged to publish excellent investigator‐initiated studies with important clues for clinical practice, 3 research from national groups 4 and/or national database analysis using artificial intelligence, meta‐analysis and systematic reviews 5–7 . We welcome with particular interest the young generation of gastroenterologists who perform translational science in different domains such as biomarkers, outcome modifying strategies, new diagnostic tools (point‐of‐care), or studies that explore alternative treatment approaches 8 . Moreover, we challenge top leaders in each field to submit relevant reviews exploring the hot topics 9 .…”