Serological Biomarkers of Extracellular Matrix Turnover and Neutrophil Activity Are Associated with Long-Term Use of Vedolizumab in Patients with Crohn's Disease

• Published in: International journal of molecular sciences 2022-07, Vol.23 (15), p.8137
• Main Authors: Alexdottir, Marta S, Bourgonje, Arno R, Karsdal, Morten A, Pehrsson, Martin, Loveikyte, Roberta, van Dullemen, Hendrik M, Visschedijk, Marijn C, Festen, Eleonora A M, Weersma, Rinse K, Faber, Klaas Nico, Dijkstra, Gerard, Mortensen, Joachim H
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal, Humanized; Biomarkers; Biomarkers - metabolism; Cadmium; Collagen; Collagen (type III); Complement C4 - metabolism; Crohn Disease - metabolism; Crohn's disease; Decision making; Elastase; Extracellular matrix; Extracellular Matrix - metabolism; Fragments; Homeostasis; Humans; Inflammation; Inflammatory bowel disease; Inflammatory bowel diseases; Leukocytes (neutrophilic); Lymphocytes T; Matrix metalloproteinase; Matrix metalloproteinases; Membrane turnover; Metalloproteinase; Monoclonal antibodies; Mucosa; Neutrophils; Patients; Serology; Serum levels; Trends; Tumor necrosis factor-TNF
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23158137

Crohn’s disease (CD) is a relapsing-remitting inflammatory disease of the gastrointestinal (GI) tract characterized by increased extracellular matrix (ECM) remodeling. The introduction of the α4β7-integrin inhibitor vedolizumab (VEDO) has improved disease management, although there is a high rate of primary non-response in patients with CD. We studied whether ECM biomarkers of neutrophil activity and mucosal damage could predict long-term response to VEDO in patients with CD. Serum levels of human neutrophil elastase (HNE)-derived fragments of calprotectin (CPa9-HNE), and matrix metalloproteinase (MMP)-derived fragments of type I (C1M), III (C3M), IV (C4M), and VI (C6Ma3) collagen, type III collagen formation (PRO-C3), basement membrane turnover (PRO-C4) and T-cell activity (C4G), were measured using protein fingerprint assays in patients with CD (n = 32) before VEDO therapy. Long-term response was defined as VEDO treatment of at least 12 months. CPa9-HNE was significantly increased at baseline in non-responders compared with responders (p < 0.05). C1M, C3M, C4M, C6Ma3, and PRO-C4 were also significantly increased at baseline in non-responders compared with responders (all p < 0.05). All biomarkers were associated with response to VEDO (all p < 0.05). To conclude, baseline levels of serum biomarkers for neutrophil activity and mucosal damage are linked to the pathology of CD, and are associated with long-term use of VEDO in patients with CD. Therefore, these biomarkers warrant further validation and could aid in therapeutic decision-making concerning vedolizumab therapy.