TY - JOUR
T1 - Novel Biomarker of Collagen Degradation Can Identify Patients Affected With Both Axial Spondyloarthritis and Crohn Disease
AU - Nielsen, Signe Holm
AU - Stahly, Andrew
AU - Regner, Emilie H.
AU - Bay-Jensen, Anne Christine
AU - Karsdal, Morten A.
AU - Kuhn, Kristine A.
N1 - Funding Information:
This work was supported by the Danish Research Foundation “Den Danske Forskningsfond” and the Danish Innovation Foundation (Innovationsfonden). 1S. Holm Nielsen, PhD, Biomedicine and Biotechnology, Technical University of Denmark, Lyngby, and ImmunoScience, Nordic Bioscience, Biomarkers and Research, Herlev, Denmark; 2A. Stahly, MD, E.H. Regner, MD, PhD, K.A. Kuhn, MD, PhD, Department of Medicine, Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; 3A.C. Bay-Jensen, PhD, M.A. Karsdal, PhD, Biomedicine and Biotechnology, Technical University of Denmark, Lyngby, Denmark. SHN, ACBJ, and MAK are full-time employees at Nordic Bioscience A/S. Nordic Bioscience is a privately-owned, small-and medium-sized enterprise 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 MAK hold stocks in Nordic Bioscience A/S. The remaining authors declare no conflicts of interest relevant to this article. Address correspondence to Dr. S. Holm Nielsen, Herlev Hovedgade 207, DK-2730 Herlev, Denmark. Email: shn@nordicbio.com. Accepted for publication July 8, 2022.
Publisher Copyright:
© 2022 The Journal of Rheumatology.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Objective. Chronic inflammatory arthritis is a hallmark of axial spondyloarthritis (axSpA), where coexistence of Crohn disease (CD) is prominent. We investigated the association between biomarkers of collagen degradation in healthy controls (HCs) and in patients with axSpA, CD, and CD and axSpA overlap (CD-axSpA), with the aim to investigate the ability of the biomarkers to identify patients with CD-axSpA. Methods. Patients with axSpA who fulfilled Assessment of Spondyloarthritis international Society criteria (n = 13), had biopsy-proven CD (n = 14), had CD-axSpA (n = 10), and HCs (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 area under the receiver-operating characteristic (AUROC) curve analysis, and Spearman correlation. Results. C4M was significantly higher in patients with CD-axSpA overlap compared to axSpA, CD, and HCs (all P < 0.001). In an AUROC analysis, C4M showed a complete separation between the patients with CD-axSpA overlap compared to HC, axSpA and CD with an area under the curve (AUC) = 1.00 (P < 0.001). No differences were found between the patient groups for C3M, C6M, and C10C. No correlations were found between the collagen biomarkers and C-reactive protein, Bath Ankylosing Spondylitis Disease Activity Index, Simple Clinical Colitis Activity Index, or Harvey-Bradshaw Index 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 HCs, and indicates excessive collagen degradation and epithelial turnover. This biomarker could potentially be used to identify patients affected by both manifestations and to guide treatment decisions.
AB - Objective. Chronic inflammatory arthritis is a hallmark of axial spondyloarthritis (axSpA), where coexistence of Crohn disease (CD) is prominent. We investigated the association between biomarkers of collagen degradation in healthy controls (HCs) and in patients with axSpA, CD, and CD and axSpA overlap (CD-axSpA), with the aim to investigate the ability of the biomarkers to identify patients with CD-axSpA. Methods. Patients with axSpA who fulfilled Assessment of Spondyloarthritis international Society criteria (n = 13), had biopsy-proven CD (n = 14), had CD-axSpA (n = 10), and HCs (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 area under the receiver-operating characteristic (AUROC) curve analysis, and Spearman correlation. Results. C4M was significantly higher in patients with CD-axSpA overlap compared to axSpA, CD, and HCs (all P < 0.001). In an AUROC analysis, C4M showed a complete separation between the patients with CD-axSpA overlap compared to HC, axSpA and CD with an area under the curve (AUC) = 1.00 (P < 0.001). No differences were found between the patient groups for C3M, C6M, and C10C. No correlations were found between the collagen biomarkers and C-reactive protein, Bath Ankylosing Spondylitis Disease Activity Index, Simple Clinical Colitis Activity Index, or Harvey-Bradshaw Index 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 HCs, and indicates excessive collagen degradation and epithelial turnover. This biomarker could potentially be used to identify patients affected by both manifestations and to guide treatment decisions.
KW - ankylosing spondylitis
KW - biomarkers
KW - collagen
KW - inflammatory bowel disease
KW - spondyloarthritis
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U2 - 10.3899/jrheum.220142
DO - 10.3899/jrheum.220142
M3 - Article
C2 - 35705233
AN - SCOPUS:85143200792
SN - 0315-162X
VL - 49
SP - 1335
EP - 1340
JO - Journal of Rheumatology
JF - Journal of Rheumatology
IS - 12
ER -