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The role of LCN2 and LCN2-MMP9 in spondylitis radiographic development: gender and HLA-B27 status differences
BACKGROUND: Male HLA-B27-positive radiographic-axial spondyloarthritis (r-axSpA) patients are prone to have severe spinal radiographic progression, but the underlying mechanisms are unclear. We recently showed that persistently elevated Lipocalin 2 (LCN2; L) reflects sacroiliac joint (SIJ) inflammat...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9264538/ https://www.ncbi.nlm.nih.gov/pubmed/35804445 http://dx.doi.org/10.1186/s13075-022-02854-2 |
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author | Tsui, Florence W. L. Lin, Aifeng Sari, Ismail Zhang, Zhenbo Pritzker, Kenneth P. H. Tsui, Hing Wo Inman, Robert D. |
author_facet | Tsui, Florence W. L. Lin, Aifeng Sari, Ismail Zhang, Zhenbo Pritzker, Kenneth P. H. Tsui, Hing Wo Inman, Robert D. |
author_sort | Tsui, Florence W. L. |
collection | PubMed |
description | BACKGROUND: Male HLA-B27-positive radiographic-axial spondyloarthritis (r-axSpA) patients are prone to have severe spinal radiographic progression, but the underlying mechanisms are unclear. We recently showed that persistently elevated Lipocalin 2 (LCN2; L) reflects sacroiliac joint (SIJ) inflammation. LCN2 binds to MMP9. Concomitant elevation of L and LCN2-MMP9 (LM) was detected in many inflammatory diseases. We asked whether L and LM play similar roles in r-axSpA pathogenesis. METHODS: We analyzed 190 axSpA patients (123 radiographic and 67 non-radiographic axSpA) who had no detectable circulating Oncostatin M, to avoid complications due to cross-talk between pathways. L and LM levels from a single blood sample of each patient were measured and were correlated with MRI and modified stoke AS (mSASS) scoring. Association of elevated L (L+) or concurrent L+ and elevated LM (LM+) patterns with B27 status and gender were assessed. RESULTS: In L+LM+ axSpA patients, both L and LM levels correlated with MRI SPARCC SIJ scores, but only LM levels correlated with MRI Berlin Spine Scores, suggesting LM is a biomarker for both SIJ and spinal inflammation. Among patients with minimal spinal ankylosis (mSASSS < 10), 65% of male r-axSpA patients are L+LM+, while 30% and 64% of female patients are L+LM+ and L+, respectively, supporting the role of LM with disease progression. In B27+ L+LM+ male patients, both L and LM (but not CRP) levels correlate with mSASSS. B27 positivity and maleness have additive effects on spondylitis progression, suggesting concurrent high L and LM elevations are associated with B27+ male patients having more significant radiographic damage. L+ B27-negative male patients or L+ female patients are more likely to have milder disease. CONCLUSION: L and LM are informative biomarkers for SIJ and spinal inflammation, as well as for ankylosing development in r-axSpA patients. Distinctive L+LM+ or L+ patterns not only could distinguish clinically aggressive vs milder course of disease, respectively, but also provide an explanation for B27-positive male patients being the most susceptible to severe ankylosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-022-02854-2. |
format | Online Article Text |
id | pubmed-9264538 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-92645382022-07-09 The role of LCN2 and LCN2-MMP9 in spondylitis radiographic development: gender and HLA-B27 status differences Tsui, Florence W. L. Lin, Aifeng Sari, Ismail Zhang, Zhenbo Pritzker, Kenneth P. H. Tsui, Hing Wo Inman, Robert D. Arthritis Res Ther Research BACKGROUND: Male HLA-B27-positive radiographic-axial spondyloarthritis (r-axSpA) patients are prone to have severe spinal radiographic progression, but the underlying mechanisms are unclear. We recently showed that persistently elevated Lipocalin 2 (LCN2; L) reflects sacroiliac joint (SIJ) inflammation. LCN2 binds to MMP9. Concomitant elevation of L and LCN2-MMP9 (LM) was detected in many inflammatory diseases. We asked whether L and LM play similar roles in r-axSpA pathogenesis. METHODS: We analyzed 190 axSpA patients (123 radiographic and 67 non-radiographic axSpA) who had no detectable circulating Oncostatin M, to avoid complications due to cross-talk between pathways. L and LM levels from a single blood sample of each patient were measured and were correlated with MRI and modified stoke AS (mSASS) scoring. Association of elevated L (L+) or concurrent L+ and elevated LM (LM+) patterns with B27 status and gender were assessed. RESULTS: In L+LM+ axSpA patients, both L and LM levels correlated with MRI SPARCC SIJ scores, but only LM levels correlated with MRI Berlin Spine Scores, suggesting LM is a biomarker for both SIJ and spinal inflammation. Among patients with minimal spinal ankylosis (mSASSS < 10), 65% of male r-axSpA patients are L+LM+, while 30% and 64% of female patients are L+LM+ and L+, respectively, supporting the role of LM with disease progression. In B27+ L+LM+ male patients, both L and LM (but not CRP) levels correlate with mSASSS. B27 positivity and maleness have additive effects on spondylitis progression, suggesting concurrent high L and LM elevations are associated with B27+ male patients having more significant radiographic damage. L+ B27-negative male patients or L+ female patients are more likely to have milder disease. CONCLUSION: L and LM are informative biomarkers for SIJ and spinal inflammation, as well as for ankylosing development in r-axSpA patients. Distinctive L+LM+ or L+ patterns not only could distinguish clinically aggressive vs milder course of disease, respectively, but also provide an explanation for B27-positive male patients being the most susceptible to severe ankylosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-022-02854-2. BioMed Central 2022-07-08 2022 /pmc/articles/PMC9264538/ /pubmed/35804445 http://dx.doi.org/10.1186/s13075-022-02854-2 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 Tsui, Florence W. L. Lin, Aifeng Sari, Ismail Zhang, Zhenbo Pritzker, Kenneth P. H. Tsui, Hing Wo Inman, Robert D. The role of LCN2 and LCN2-MMP9 in spondylitis radiographic development: gender and HLA-B27 status differences |
title | The role of LCN2 and LCN2-MMP9 in spondylitis radiographic development: gender and HLA-B27 status differences |
title_full | The role of LCN2 and LCN2-MMP9 in spondylitis radiographic development: gender and HLA-B27 status differences |
title_fullStr | The role of LCN2 and LCN2-MMP9 in spondylitis radiographic development: gender and HLA-B27 status differences |
title_full_unstemmed | The role of LCN2 and LCN2-MMP9 in spondylitis radiographic development: gender and HLA-B27 status differences |
title_short | The role of LCN2 and LCN2-MMP9 in spondylitis radiographic development: gender and HLA-B27 status differences |
title_sort | role of lcn2 and lcn2-mmp9 in spondylitis radiographic development: gender and hla-b27 status differences |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9264538/ https://www.ncbi.nlm.nih.gov/pubmed/35804445 http://dx.doi.org/10.1186/s13075-022-02854-2 |
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