320 Figure 1 | Schematic representation of the extracellular matrix (ECM) composition of the intestinal mucosa. The ECM can roughly be divided into two layers: the basement membrane (BM) and interstitial matrix (IM). The BM is mainly composed of type IV collagen, which are networking forming collagens. The IM primarily consists of type I and type III collagens, which are fibrillar collagens, as well as type VI collagens, which consists of beaded filaments. As fragments of intestinal collagens derived from an increased proteolytic activity are released into the systemic circulation, they can be measured in blood and potentially serve as serological biomarkers for stricturing and/or penetrating disease in patients with CD.5 For that purpose, protein fingerprint assays that quantify specific neo-epitope fragments of collagen formation and degradation, including MMP- and granzyme-B derived fragments of type I, III, IV, and VI collagens, have recently been developed and validated in a variety of (fibrotic) diseases.13-19 Previously, specific biomarkers of collagen formation and degradation were demonstrated to be strongly associated with CD, as well as with CD disease activity, disease behavior, and response to biological therapy.20-23 For instance, an imbalance in type III collagen formation and degradation showed potential as a biomarker for penetrating CD and as a monitoring tool for the dynamics of mucosal damage and healing.23,24 Although these results are promising, further validation studies are warranted, together with an assessment of these biomarkers for their ability to predict future disease course. Importantly, the latter goal may help to early detect and monitor disease complications in CD, thereby enabling prompt therapeutic intervention and prevention of severe disease. In this study, we aimed to evaluate the potential of circulating collagen formation and degradation fragments as discriminative biomarkers for Montreal disease behavior subclasses in patients with CD. Furthermore, we aimed to determine associations of these biomarkers with inflammatory disease activity, and to assess their predictive value in relation to the risk of progression of stricturing and penetrating disease and the risk of future surgical interventions. Chapter 10
RkJQdWJsaXNoZXIy MjY0ODMw