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Research ArticleAccepted Article

Novel Biomarker of Collagen Degradation can Identify Patients Affected with both Axial Spondyloarthritis and Crohn's Disease

Signe Holm Nielsen, Andrew Stahly, Emilie H. Regner, Anne-Christine Bay-Jensen, Morten Karsdal and Kristine A. Kuhn
The Journal of Rheumatology June 2022, jrheum.220142; DOI: https://doi.org/10.3899/jrheum.220142
Signe Holm Nielsen
Sources of Funding: This work was supported by the Danish Research Foundation "Den Danske Forskningsfond" and the Danish Innovation Foundation (Innovationsfonden). Biomedicine and Biotechnology, Technical University of Denmark, Lyngby, Denmark; Department of Medicine, Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO. Conflict of interest: SHN, ACBJ and MAK are full-time employees at Nordic Bioscience A/S. Nordic Bioscience is a privately-owned, small–medium size enterprise (SME) partly focused on the development of biomarkers. None of the authors received fees, bonuses or other benefits for the work described in the manuscript. SHN, ACBJ and MK hold stocks in Nordic Bioscience A/S. Corresponding author: Signe Holm Nielsen, Herlev Hovedgade 207, DK-2730 Herlev, Denmark, E-mail: shn@nordicbio.com
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Andrew Stahly
Sources of Funding: This work was supported by the Danish Research Foundation "Den Danske Forskningsfond" and the Danish Innovation Foundation (Innovationsfonden). Biomedicine and Biotechnology, Technical University of Denmark, Lyngby, Denmark; Department of Medicine, Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO. Conflict of interest: SHN, ACBJ and MAK are full-time employees at Nordic Bioscience A/S. Nordic Bioscience is a privately-owned, small–medium size enterprise (SME) partly focused on the development of biomarkers. None of the authors received fees, bonuses or other benefits for the work described in the manuscript. SHN, ACBJ and MK hold stocks in Nordic Bioscience A/S. Corresponding author: Signe Holm Nielsen, Herlev Hovedgade 207, DK-2730 Herlev, Denmark, E-mail: shn@nordicbio.com
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Emilie H. Regner
Sources of Funding: This work was supported by the Danish Research Foundation "Den Danske Forskningsfond" and the Danish Innovation Foundation (Innovationsfonden). Biomedicine and Biotechnology, Technical University of Denmark, Lyngby, Denmark; Department of Medicine, Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO. Conflict of interest: SHN, ACBJ and MAK are full-time employees at Nordic Bioscience A/S. Nordic Bioscience is a privately-owned, small–medium size enterprise (SME) partly focused on the development of biomarkers. None of the authors received fees, bonuses or other benefits for the work described in the manuscript. SHN, ACBJ and MK hold stocks in Nordic Bioscience A/S. Corresponding author: Signe Holm Nielsen, Herlev Hovedgade 207, DK-2730 Herlev, Denmark, E-mail: shn@nordicbio.com
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Anne-Christine Bay-Jensen
Sources of Funding: This work was supported by the Danish Research Foundation "Den Danske Forskningsfond" and the Danish Innovation Foundation (Innovationsfonden). Biomedicine and Biotechnology, Technical University of Denmark, Lyngby, Denmark; Department of Medicine, Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO. Conflict of interest: SHN, ACBJ and MAK are full-time employees at Nordic Bioscience A/S. Nordic Bioscience is a privately-owned, small–medium size enterprise (SME) partly focused on the development of biomarkers. None of the authors received fees, bonuses or other benefits for the work described in the manuscript. SHN, ACBJ and MK hold stocks in Nordic Bioscience A/S. Corresponding author: Signe Holm Nielsen, Herlev Hovedgade 207, DK-2730 Herlev, Denmark, E-mail: shn@nordicbio.com
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Morten Karsdal
Sources of Funding: This work was supported by the Danish Research Foundation "Den Danske Forskningsfond" and the Danish Innovation Foundation (Innovationsfonden). Biomedicine and Biotechnology, Technical University of Denmark, Lyngby, Denmark; Department of Medicine, Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO. Conflict of interest: SHN, ACBJ and MAK are full-time employees at Nordic Bioscience A/S. Nordic Bioscience is a privately-owned, small–medium size enterprise (SME) partly focused on the development of biomarkers. None of the authors received fees, bonuses or other benefits for the work described in the manuscript. SHN, ACBJ and MK hold stocks in Nordic Bioscience A/S. Corresponding author: Signe Holm Nielsen, Herlev Hovedgade 207, DK-2730 Herlev, Denmark, E-mail: shn@nordicbio.com
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Kristine A. Kuhn
Sources of Funding: This work was supported by the Danish Research Foundation "Den Danske Forskningsfond" and the Danish Innovation Foundation (Innovationsfonden). Biomedicine and Biotechnology, Technical University of Denmark, Lyngby, Denmark; Department of Medicine, Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO. Conflict of interest: SHN, ACBJ and MAK are full-time employees at Nordic Bioscience A/S. Nordic Bioscience is a privately-owned, small–medium size enterprise (SME) partly focused on the development of biomarkers. None of the authors received fees, bonuses or other benefits for the work described in the manuscript. SHN, ACBJ and MK hold stocks in Nordic Bioscience A/S. Corresponding author: Signe Holm Nielsen, Herlev Hovedgade 207, DK-2730 Herlev, Denmark, E-mail: shn@nordicbio.com
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Abstract

Objective Chronic inflammatory arthritis is a hallmark of axial spondyloarthritis (axSpA), where co-existence of Crohn's Disease (CD) is prominent. We investigated the association between biomarkers of collagen degradation in healthy controls (HC) and patients with axSpA, CD and CD-axSpA overlap, with the aim to investigate the biomarkers' ability to identify patients with CD-axSpA overlap.

Methods Patients with axSpA fulfilling ASAS criteria (n=13), biopsy-proven CD (n=14), subjects with axSpA and CD overlap (n=10) and healthy controls (n=11) undergoing standard of care colonoscopies were included in the study. The collagen biomarkers measuring type III, IV, VI and X collagen (C3M, C4M, C6M and C10C, respectively) were measured in plasma samples from all subject groups. Statistical analysis was performed using an ANCOVA adjusted for age, an AUROC analysis and spearman correlations.

Results C4M was significantly higher in patients with CD-axSpA overlap compared to axSpA, CD and HCs (all p<0.0001). In an AUROC analysis, C4M showed a complete separation between the patients with CD-axSpA overlap compared to HC, axSpA and CD with an AUC=1.00; p=0.0001. No differences were found between the patient groups for C3M, C6M and C10C. 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 CD-axSpA overlap, compared to axSpA, 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.

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The Journal of Rheumatology
Vol. 49, Issue 8
1 Aug 2022
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Accepted manuscript
Novel Biomarker of Collagen Degradation can Identify Patients Affected with both Axial Spondyloarthritis and Crohn's Disease
Signe Holm Nielsen, Andrew Stahly, Emilie H. Regner, Anne-Christine Bay-Jensen, Morten Karsdal, Kristine A. Kuhn
The Journal of Rheumatology Jun 2022, jrheum.220142; DOI: 10.3899/jrheum.220142

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Accepted manuscript
Novel Biomarker of Collagen Degradation can Identify Patients Affected with both Axial Spondyloarthritis and Crohn's Disease
Signe Holm Nielsen, Andrew Stahly, Emilie H. Regner, Anne-Christine Bay-Jensen, Morten Karsdal, Kristine A. Kuhn
The Journal of Rheumatology Jun 2022, jrheum.220142; DOI: 10.3899/jrheum.220142
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