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Extracellular matrix protein turnover markers are associated with axial spondyloarthritis—a comparison with postpartum women and other non-axial spondyloarthritis controls with or without back pain

BACKGROUND: Axial spondyloarthritis (axSpA) is a common chronic inflammatory disease, associated with extracellular matrix (ECM) remodeling of the cartilage, bone, and connective tissues. The primary symptom of axSpA is back pain, caused by inflammation. However, there is a medical need to truly ide...

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Autores principales: Port, Helena, Nielsen, Signe Holm, Madsen, Sofie Falkenløve, Bay-Jensen, Anne-Christine, Karsdal, Morten, Seven, Sengül, Sørensen, Inge Juul, Morsel-Carlsen, Lone, Østergaard, Mikkel, Pedersen, Susanne Juhl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219155/
https://www.ncbi.nlm.nih.gov/pubmed/35739562
http://dx.doi.org/10.1186/s13075-022-02839-1
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author Port, Helena
Nielsen, Signe Holm
Madsen, Sofie Falkenløve
Bay-Jensen, Anne-Christine
Karsdal, Morten
Seven, Sengül
Sørensen, Inge Juul
Morsel-Carlsen, Lone
Østergaard, Mikkel
Pedersen, Susanne Juhl
author_facet Port, Helena
Nielsen, Signe Holm
Madsen, Sofie Falkenløve
Bay-Jensen, Anne-Christine
Karsdal, Morten
Seven, Sengül
Sørensen, Inge Juul
Morsel-Carlsen, Lone
Østergaard, Mikkel
Pedersen, Susanne Juhl
author_sort Port, Helena
collection PubMed
description BACKGROUND: Axial spondyloarthritis (axSpA) is a common chronic inflammatory disease, associated with extracellular matrix (ECM) remodeling of the cartilage, bone, and connective tissues. The primary symptom of axSpA is back pain, caused by inflammation. However, there is a medical need to truly identify patients with axSpA from other subjects with buttock or low back pain attributable to other reasons. We aimed to investigate circulating biomarkers of ECM/inflammation (MMP-degraded type I (C1M), II (C2M, T2CM), III (C3M), IV (C4M), VI (C6M), and X (C10C, COL10NC) collagens, CRPM, PROM and VICM) and ECM formation of type II (PRO-C2), III (PRO-C3), IV (PRO-C4), and VI (PRO-C6) collagens as potential biomarkers to identify patients with axSpA. METHODS: We measured biomarkers from a cross-sectional study with 204 participants by enzyme-linked immunosorbent assay (ELISA). The study included axSpA patients (N = 41), women with postpartum buttock/pelvic pain (N = 46), disc herniation (N = 25), and a group of healthy subjects (including women without postpartum pelvic pain (N = 14), subjects with various types of physical strain (cleaning staff (N = 26) long-distance runners (N = 23)), and healthy men (N = 29)). Differences between the groups were calculated by ANCOVA and AUC, while Spearman’s correlations were performed with ECM biomarkers and clinical scores. RESULTS: Patients with axSpA expressed significantly higher levels of C1M, C4M, and VICM (p < 0.05-p < 0.0001) compared to all the non-axSpA control groups. Further, C6M and PRO-C4 were significantly higher in patients with axSpA (both p < 0.0001) compared to women with postpartum pelvic pain and healthy subjects, whereas PRO-C3 was significantly lower compared to healthy subjects (p = 0.01). The best ECM common biomarker to differentiate between axSpA and the non-axSpA control groups was PRO-C4 (AUC ≥ 0.75; specificity ≥ 0.79, sensitivity = 0.65). Mild correlations were observed between collagen turnover and inflammation biomarkers and CRP and MRI (ρ ≥ 0.3; p < 0.05-p < 0.001). CONCLUSIONS: Biomarkers of type I, IV, and VI collagen and biomarkers of inflammation showed an altered turnover in patients with axSpA compared with the non-axSpA control groups. Such biomarkers may be useful in combination with MRI or independently to separate patients with axSpA from other back pain conditions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-022-02839-1.
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spelling pubmed-92191552022-06-24 Extracellular matrix protein turnover markers are associated with axial spondyloarthritis—a comparison with postpartum women and other non-axial spondyloarthritis controls with or without back pain Port, Helena Nielsen, Signe Holm Madsen, Sofie Falkenløve Bay-Jensen, Anne-Christine Karsdal, Morten Seven, Sengül Sørensen, Inge Juul Morsel-Carlsen, Lone Østergaard, Mikkel Pedersen, Susanne Juhl Arthritis Res Ther Research BACKGROUND: Axial spondyloarthritis (axSpA) is a common chronic inflammatory disease, associated with extracellular matrix (ECM) remodeling of the cartilage, bone, and connective tissues. The primary symptom of axSpA is back pain, caused by inflammation. However, there is a medical need to truly identify patients with axSpA from other subjects with buttock or low back pain attributable to other reasons. We aimed to investigate circulating biomarkers of ECM/inflammation (MMP-degraded type I (C1M), II (C2M, T2CM), III (C3M), IV (C4M), VI (C6M), and X (C10C, COL10NC) collagens, CRPM, PROM and VICM) and ECM formation of type II (PRO-C2), III (PRO-C3), IV (PRO-C4), and VI (PRO-C6) collagens as potential biomarkers to identify patients with axSpA. METHODS: We measured biomarkers from a cross-sectional study with 204 participants by enzyme-linked immunosorbent assay (ELISA). The study included axSpA patients (N = 41), women with postpartum buttock/pelvic pain (N = 46), disc herniation (N = 25), and a group of healthy subjects (including women without postpartum pelvic pain (N = 14), subjects with various types of physical strain (cleaning staff (N = 26) long-distance runners (N = 23)), and healthy men (N = 29)). Differences between the groups were calculated by ANCOVA and AUC, while Spearman’s correlations were performed with ECM biomarkers and clinical scores. RESULTS: Patients with axSpA expressed significantly higher levels of C1M, C4M, and VICM (p < 0.05-p < 0.0001) compared to all the non-axSpA control groups. Further, C6M and PRO-C4 were significantly higher in patients with axSpA (both p < 0.0001) compared to women with postpartum pelvic pain and healthy subjects, whereas PRO-C3 was significantly lower compared to healthy subjects (p = 0.01). The best ECM common biomarker to differentiate between axSpA and the non-axSpA control groups was PRO-C4 (AUC ≥ 0.75; specificity ≥ 0.79, sensitivity = 0.65). Mild correlations were observed between collagen turnover and inflammation biomarkers and CRP and MRI (ρ ≥ 0.3; p < 0.05-p < 0.001). CONCLUSIONS: Biomarkers of type I, IV, and VI collagen and biomarkers of inflammation showed an altered turnover in patients with axSpA compared with the non-axSpA control groups. Such biomarkers may be useful in combination with MRI or independently to separate patients with axSpA from other back pain conditions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-022-02839-1. BioMed Central 2022-06-23 2022 /pmc/articles/PMC9219155/ /pubmed/35739562 http://dx.doi.org/10.1186/s13075-022-02839-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Port, Helena
Nielsen, Signe Holm
Madsen, Sofie Falkenløve
Bay-Jensen, Anne-Christine
Karsdal, Morten
Seven, Sengül
Sørensen, Inge Juul
Morsel-Carlsen, Lone
Østergaard, Mikkel
Pedersen, Susanne Juhl
Extracellular matrix protein turnover markers are associated with axial spondyloarthritis—a comparison with postpartum women and other non-axial spondyloarthritis controls with or without back pain
title Extracellular matrix protein turnover markers are associated with axial spondyloarthritis—a comparison with postpartum women and other non-axial spondyloarthritis controls with or without back pain
title_full Extracellular matrix protein turnover markers are associated with axial spondyloarthritis—a comparison with postpartum women and other non-axial spondyloarthritis controls with or without back pain
title_fullStr Extracellular matrix protein turnover markers are associated with axial spondyloarthritis—a comparison with postpartum women and other non-axial spondyloarthritis controls with or without back pain
title_full_unstemmed Extracellular matrix protein turnover markers are associated with axial spondyloarthritis—a comparison with postpartum women and other non-axial spondyloarthritis controls with or without back pain
title_short Extracellular matrix protein turnover markers are associated with axial spondyloarthritis—a comparison with postpartum women and other non-axial spondyloarthritis controls with or without back pain
title_sort extracellular matrix protein turnover markers are associated with axial spondyloarthritis—a comparison with postpartum women and other non-axial spondyloarthritis controls with or without back pain
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219155/
https://www.ncbi.nlm.nih.gov/pubmed/35739562
http://dx.doi.org/10.1186/s13075-022-02839-1
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