POS0966 IDENTIFICATION OF PATIENTS AFFECTED WITH ANKYLOSING SPONDYLITIS AND INFLAMMATORY BOWEL DISEASE OVERLAP USING COLLAGEN BIOMARKERS
Authors: S. Holm Nielsen, A. Stahly, E. H. Regner, A. C. Bay-Jensen, M. Karsdal, K. A. Kuhn
Journal: Annals of the Rheumatic Diseases (2021)

Background: Chronic inflammatory arthritis is a hallmark of Ankylosing Spondylitis (AS), where co-existence of inflammatory bowel disease, such as Crohn’s Disease (CD) is prominent. The clinical overlap of AS and CD has raised the hypothesis that these conditions may have similar pathophysiological mechanisms. Both indications are characterized by an altered extracellular matrix turnover, where particularly collagens are remodeled. Objectives: We investigated the association between biomarkers of collagen degradation in healthy controls and patients with AS, CD and AS/CD overlap, with the aim to investigate the biomarkers’ ability to identify patients with AS/CD overlap. Methods: Patients with AS fulfilling ASAS criteria (n=13), biopsy-proven CD (n=14), subjects with AS and CD overlap (n=10) and healthy controls (n=11) undergoing standard of care colonoscopies were included in the study. The collagen degradation biomarkers measuring type III, IV, VI and X collagen (C3M, C4M, C6M and C10C, respectively) were measured in EDTA plasma samples from all subject groups. Biomarkers were measured by competitive ELISAs. Statistical analysis was performed using an ANCOVA adjusted for age, an AUROC analysis and spearman correlations. Results: The collagen biomarker C4M was significantly higher in patients with AS/CD overlap compared to AS, CD and HCs (all p&lt;0.0001, Figure 1A). The blood levels of C4M in AS patients were significantly lower than HC (p=0.0003), while CD also showed a lower level compared to HC though not significant (p=0.0798). No difference was found between AS and CD alone. In an AUROC analysis, C4M showed a complete separation between the patients with AS/CD overlap compared to HC, AS and CD with an AUC=1.00; p=0.0001. No differences were found between the patient groups for C3M, C6M and C10C (Figure 1, B-D). 91.3 % of patients with AS, 92.8% of patients with CD and 60 % of patients with AS and IBD overlap were actively treated with TNF-α inhibitors, which may explain the suppression of the collagen degradation biomarker levels in AS, CD and AS/IBD overlap compared to healthy controls[1,2]. No correlations were found between the collagen biomarkers and CRP, BASDAI, SCCAI or HBI scores. Conclusion: Degradation of type IV collagen quantified by C4M showed a complete separation of patients with AS/IBD overlap, compared to AS, CD and HC patients, which indicates an excessive collagen degradation and epithelial turnover. This biomarker could potentially be used to identify patients affected by both manifestations, and guide treatment decisions. References: [1]van Haaften WT, Mortensen JH, Dige AK, Grønbæk H, Hvas CL, Bay-Jensen AC, et al. Serological Biomarkers of Tissue Turnover Identify Responders to Anti-TNF Therapy in Crohn’s Disease: A Pilot Study. Clin Transl Gastroenterol. 2020;11:e00217. [2]Siebuhr AS, Bay-Jensen AC, Karsdal MA, Lories RJ, de Vlam K. CRP and a biomarker of type I collagen degradation, C1M, can differentiate anti-inflammatory treatment response in ankylosing spondylitis. Biomark Med. 2016;10:197–208. Figure 1. Levels of C4M (A), C3M (B), C6M (C) and C10C (D) in EDTA plasma from patients diagnosed with AS (n=13), CD (n=14), AS and CD overlap (n=10) and HC (n=11). Graphs are presented as Tukey box plots. Statistical significance: ****p&lt;0.0001. Disclosure of Interests: Signe Holm Nielsen Employee of: Full time PostDoc at Nordic Bioscience and Technical University of Denmark, Andrew Stahly: None declared, Emilie H. Regner: None declared, Anne-Christine Bay-Jensen Shareholder of: Stocks at Nordic Bioscience, Employee of: Full-time employee at Nordic Bioscience, Morten Karsdal Shareholder of: Stocks at Nordic Bioscience, Employee of: Full-time employee at Nordic Bioscience, Kristine A. Kuhn: None declared.