Misbalance in type III collagen formation/degradation as a novel serological biomarker for penetrating (Montreal B3) Crohn's disease

Background: Misbalances in extracellular matrix turnover are key factors in the development of stricturing (Montreal B2) and penetrating (Montreal B3) Crohn's disease. Aim: To determine whether serological markers for collagen formation and degradation could serve as biomarkers for complications of Crohn's disease. Methods: Serum biomarkers for type I, III, V and VI collagen formation (P1NP, ProC3, Pro-C5, Pro-C6) and matrix metalloproteinase mediated degradation (C1M, C3M, C5M and C6M) were measured in a retrospective, single centre cohort of 112 patients with Crohn's disease in the terminal ileum (nonstricturing/nonpenetrating: n=40, stricturing: n=55, penetrating: n=17) and 24 healthy controls. Active inflammation was defined as CRP >5 mg/L. Results: C3M and Pro-C5 levels were higher in penetrating vs nonpenetrating/nonstricturing and stricturing disease (33.6 +/- 5 vs 25.8 +/- 2.2 [P=.004] and 27.2 +/- 2.3 [P=.018] nmol/L C3M, 1262.7 +/- 259.4 vs 902.9 +/- 109.9 [P=.005] and 953.0 +/- 106.4 [P=.015]nmol/L Pro-C5). C1M (71.2 +/- 26.1 vs 46.2 +/- 6.2 nmol/L [P Conclusions: Serological biomarkers show that penetrating Crohn's disease is characterised by increased matrix metalloproteinase-9 degraded type III collagen and formation of type V collagen. Active inflammation in Crohn's disease is characterised by increased formation of type V collagen and increased matrix metalloproteinase mediated breakdown of type I, III collagen. Pro-C3/C3M-ratios are superior in differentiating between penetrating Crohn's disease vs inflammatory and stricturing Crohn's disease