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Angiopoietin-2/-1 ratios and MMP-3 levels as an early warning sign for the presence of giant cell arteritis in patients with polymyalgia rheumatica

BACKGROUND: Diagnosing patients with giant cell arteritis (GCA) remains difficult. Due to its non-specific symptoms, it is challenging to identify GCA in patients presenting with symptoms of polymyalgia rheumatica (PMR), which is a more common disease. Also, commonly used acute-phase markers CRP and...

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Autores principales: van Sleen, Yannick, Therkildsen, Philip, Nielsen, Berit Dalsgaard, van der Geest, Kornelis S. M., Hansen, Ib, Heeringa, Peter, Posthumus, Marcel D., Sandovici, Maria, Toonen, Erik J. M., Zijlstra, Jannik, Boots, Annemieke M. H., Hauge, Ellen-Margrethe, Brouwer, Elisabeth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8900446/
https://www.ncbi.nlm.nih.gov/pubmed/35255968
http://dx.doi.org/10.1186/s13075-022-02754-5
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author van Sleen, Yannick
Therkildsen, Philip
Nielsen, Berit Dalsgaard
van der Geest, Kornelis S. M.
Hansen, Ib
Heeringa, Peter
Posthumus, Marcel D.
Sandovici, Maria
Toonen, Erik J. M.
Zijlstra, Jannik
Boots, Annemieke M. H.
Hauge, Ellen-Margrethe
Brouwer, Elisabeth
author_facet van Sleen, Yannick
Therkildsen, Philip
Nielsen, Berit Dalsgaard
van der Geest, Kornelis S. M.
Hansen, Ib
Heeringa, Peter
Posthumus, Marcel D.
Sandovici, Maria
Toonen, Erik J. M.
Zijlstra, Jannik
Boots, Annemieke M. H.
Hauge, Ellen-Margrethe
Brouwer, Elisabeth
author_sort van Sleen, Yannick
collection PubMed
description BACKGROUND: Diagnosing patients with giant cell arteritis (GCA) remains difficult. Due to its non-specific symptoms, it is challenging to identify GCA in patients presenting with symptoms of polymyalgia rheumatica (PMR), which is a more common disease. Also, commonly used acute-phase markers CRP and ESR fail to discriminate GCA patients from PMR and (infectious) mimicry patients. Therefore, we investigated biomarkers reflecting vessel wall inflammation for their utility in the accurate diagnosis of GCA in two international cohorts. METHODS: Treatment-naïve GCA patients participated in the Aarhus AGP cohort (N = 52) and the Groningen GPS cohort (N = 48). The AGP and GPS biomarker levels and symptoms were compared to patients presenting phenotypically as isolated PMR, infectious mimicry controls and healthy controls (HCs). Serum/plasma levels of 12 biomarkers were measured by ELISA or Luminex. RESULTS: In both the AGP and the GPS cohort, we found that weight loss, elevated erythrocyte sedimentation rate (ESR) and higher angiopoietin-2/-1 ratios but lower matrix metalloproteinase (MMP)-3 levels identify concomitant GCA in PMR patients. In addition, we confirmed that elevated platelet counts are characteristic of GCA but not of GCA mimicry controls and that low MMP-3 and proteinase 3 (PR3) levels may help to discriminate GCA from infections. CONCLUSION: This study, performed in two independent international cohorts, consistently shows the potential of angiopoietin-2/-1 ratios and MMP-3 levels to identify GCA in patients presenting with PMR. These biomarkers may be used to select which PMR patients require further diagnostic workup. Platelet counts may be used to discriminate GCA from GCA look-alike patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-022-02754-5.
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spelling pubmed-89004462022-03-17 Angiopoietin-2/-1 ratios and MMP-3 levels as an early warning sign for the presence of giant cell arteritis in patients with polymyalgia rheumatica van Sleen, Yannick Therkildsen, Philip Nielsen, Berit Dalsgaard van der Geest, Kornelis S. M. Hansen, Ib Heeringa, Peter Posthumus, Marcel D. Sandovici, Maria Toonen, Erik J. M. Zijlstra, Jannik Boots, Annemieke M. H. Hauge, Ellen-Margrethe Brouwer, Elisabeth Arthritis Res Ther Research BACKGROUND: Diagnosing patients with giant cell arteritis (GCA) remains difficult. Due to its non-specific symptoms, it is challenging to identify GCA in patients presenting with symptoms of polymyalgia rheumatica (PMR), which is a more common disease. Also, commonly used acute-phase markers CRP and ESR fail to discriminate GCA patients from PMR and (infectious) mimicry patients. Therefore, we investigated biomarkers reflecting vessel wall inflammation for their utility in the accurate diagnosis of GCA in two international cohorts. METHODS: Treatment-naïve GCA patients participated in the Aarhus AGP cohort (N = 52) and the Groningen GPS cohort (N = 48). The AGP and GPS biomarker levels and symptoms were compared to patients presenting phenotypically as isolated PMR, infectious mimicry controls and healthy controls (HCs). Serum/plasma levels of 12 biomarkers were measured by ELISA or Luminex. RESULTS: In both the AGP and the GPS cohort, we found that weight loss, elevated erythrocyte sedimentation rate (ESR) and higher angiopoietin-2/-1 ratios but lower matrix metalloproteinase (MMP)-3 levels identify concomitant GCA in PMR patients. In addition, we confirmed that elevated platelet counts are characteristic of GCA but not of GCA mimicry controls and that low MMP-3 and proteinase 3 (PR3) levels may help to discriminate GCA from infections. CONCLUSION: This study, performed in two independent international cohorts, consistently shows the potential of angiopoietin-2/-1 ratios and MMP-3 levels to identify GCA in patients presenting with PMR. These biomarkers may be used to select which PMR patients require further diagnostic workup. Platelet counts may be used to discriminate GCA from GCA look-alike patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-022-02754-5. BioMed Central 2022-03-07 2022 /pmc/articles/PMC8900446/ /pubmed/35255968 http://dx.doi.org/10.1186/s13075-022-02754-5 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
van Sleen, Yannick
Therkildsen, Philip
Nielsen, Berit Dalsgaard
van der Geest, Kornelis S. M.
Hansen, Ib
Heeringa, Peter
Posthumus, Marcel D.
Sandovici, Maria
Toonen, Erik J. M.
Zijlstra, Jannik
Boots, Annemieke M. H.
Hauge, Ellen-Margrethe
Brouwer, Elisabeth
Angiopoietin-2/-1 ratios and MMP-3 levels as an early warning sign for the presence of giant cell arteritis in patients with polymyalgia rheumatica
title Angiopoietin-2/-1 ratios and MMP-3 levels as an early warning sign for the presence of giant cell arteritis in patients with polymyalgia rheumatica
title_full Angiopoietin-2/-1 ratios and MMP-3 levels as an early warning sign for the presence of giant cell arteritis in patients with polymyalgia rheumatica
title_fullStr Angiopoietin-2/-1 ratios and MMP-3 levels as an early warning sign for the presence of giant cell arteritis in patients with polymyalgia rheumatica
title_full_unstemmed Angiopoietin-2/-1 ratios and MMP-3 levels as an early warning sign for the presence of giant cell arteritis in patients with polymyalgia rheumatica
title_short Angiopoietin-2/-1 ratios and MMP-3 levels as an early warning sign for the presence of giant cell arteritis in patients with polymyalgia rheumatica
title_sort angiopoietin-2/-1 ratios and mmp-3 levels as an early warning sign for the presence of giant cell arteritis in patients with polymyalgia rheumatica
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8900446/
https://www.ncbi.nlm.nih.gov/pubmed/35255968
http://dx.doi.org/10.1186/s13075-022-02754-5
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