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A matrix metalloproteinase-generated neoepitope of CRP can identify knee and multi-joint inflammation in osteoarthritis
OBJECTIVE: To compare C-reactive protein (CRP) and matrix metalloproteinase-generated neoepitope of CRP (CRPM) as biomarkers of inflammation and radiographic severity in patients with knee osteoarthritis. METHODS: Participants with symptomatic osteoarthritis (n=25) of at least one knee underwent kne...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407005/ https://www.ncbi.nlm.nih.gov/pubmed/34465395 http://dx.doi.org/10.1186/s13075-021-02610-y |
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author | Alexander, Louie C. McHorse, Grant Huebner, Janet L. Bay-Jensen, Anne-Christine Karsdal, Morten A. Kraus, Virginia B. |
author_facet | Alexander, Louie C. McHorse, Grant Huebner, Janet L. Bay-Jensen, Anne-Christine Karsdal, Morten A. Kraus, Virginia B. |
author_sort | Alexander, Louie C. |
collection | PubMed |
description | OBJECTIVE: To compare C-reactive protein (CRP) and matrix metalloproteinase-generated neoepitope of CRP (CRPM) as biomarkers of inflammation and radiographic severity in patients with knee osteoarthritis. METHODS: Participants with symptomatic osteoarthritis (n=25) of at least one knee underwent knee radiographic imaging and radionuclide etarfolatide imaging to quantify inflammation of the knees and other appendicular joints. For purposes of statistical analysis, semi-quantitative etarfolatide and radiographic imaging scores were summed across the knees; etarfolatide scores were also summed across all joints to provide a multi-joint synovitis measure. Multiple inflammation and collagen-related biomarkers were measured by ELISA including CRP, CRPM, MMP-generated neoepitopes of type I collagen and type III collagen in serum (n=25), and CD163 in serum (n=25) and synovial fluid (n=18). RESULTS: BMI was associated with CRP (p=0.001), but not CRPM (p=0.753). Adjusting for BMI, CRP was associated with radiographic knee osteophyte score (p=0.002), while CRPM was associated with synovitis of the knee (p=0.017), synovitis of multiple joints (p=0.008), and macrophage marker CD163 in serum (p=0.009) and synovial fluid (p=0.03). CRP correlated with MMP-generated neoepitope of type I collagen in serum (p=0.045), and CRPM correlated with MMP-generated neoepitope of type III collagen in serum (p<0.0001). No biomarkers correlated with age, knee pain, or WOMAC pain. CONCLUSIONS: To our knowledge, this is the first time that CRPM has been shown to be associated with knee and multi-joint inflammation based on objective imaging (etarfolatide) and biomarker (CD163) measures. These results demonstrate the capability of biomarker measurements to reflect complex biological processes and for neoepitope markers to more distinctly reflect acute processes than their precursor proteins. CRPM is a promising biomarker of local and systemic inflammation in knee OA that is associated with cartilage degradation and is independent of BMI. CRPM is a potential molecular biomarker alternative to etarfolatide imaging for quantitative assessment of joint inflammation. |
format | Online Article Text |
id | pubmed-8407005 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-84070052021-09-01 A matrix metalloproteinase-generated neoepitope of CRP can identify knee and multi-joint inflammation in osteoarthritis Alexander, Louie C. McHorse, Grant Huebner, Janet L. Bay-Jensen, Anne-Christine Karsdal, Morten A. Kraus, Virginia B. Arthritis Res Ther Research Article OBJECTIVE: To compare C-reactive protein (CRP) and matrix metalloproteinase-generated neoepitope of CRP (CRPM) as biomarkers of inflammation and radiographic severity in patients with knee osteoarthritis. METHODS: Participants with symptomatic osteoarthritis (n=25) of at least one knee underwent knee radiographic imaging and radionuclide etarfolatide imaging to quantify inflammation of the knees and other appendicular joints. For purposes of statistical analysis, semi-quantitative etarfolatide and radiographic imaging scores were summed across the knees; etarfolatide scores were also summed across all joints to provide a multi-joint synovitis measure. Multiple inflammation and collagen-related biomarkers were measured by ELISA including CRP, CRPM, MMP-generated neoepitopes of type I collagen and type III collagen in serum (n=25), and CD163 in serum (n=25) and synovial fluid (n=18). RESULTS: BMI was associated with CRP (p=0.001), but not CRPM (p=0.753). Adjusting for BMI, CRP was associated with radiographic knee osteophyte score (p=0.002), while CRPM was associated with synovitis of the knee (p=0.017), synovitis of multiple joints (p=0.008), and macrophage marker CD163 in serum (p=0.009) and synovial fluid (p=0.03). CRP correlated with MMP-generated neoepitope of type I collagen in serum (p=0.045), and CRPM correlated with MMP-generated neoepitope of type III collagen in serum (p<0.0001). No biomarkers correlated with age, knee pain, or WOMAC pain. CONCLUSIONS: To our knowledge, this is the first time that CRPM has been shown to be associated with knee and multi-joint inflammation based on objective imaging (etarfolatide) and biomarker (CD163) measures. These results demonstrate the capability of biomarker measurements to reflect complex biological processes and for neoepitope markers to more distinctly reflect acute processes than their precursor proteins. CRPM is a promising biomarker of local and systemic inflammation in knee OA that is associated with cartilage degradation and is independent of BMI. CRPM is a potential molecular biomarker alternative to etarfolatide imaging for quantitative assessment of joint inflammation. BioMed Central 2021-08-31 2021 /pmc/articles/PMC8407005/ /pubmed/34465395 http://dx.doi.org/10.1186/s13075-021-02610-y Text en © The Author(s) 2021 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 Article Alexander, Louie C. McHorse, Grant Huebner, Janet L. Bay-Jensen, Anne-Christine Karsdal, Morten A. Kraus, Virginia B. A matrix metalloproteinase-generated neoepitope of CRP can identify knee and multi-joint inflammation in osteoarthritis |
title | A matrix metalloproteinase-generated neoepitope of CRP can identify knee and multi-joint inflammation in osteoarthritis |
title_full | A matrix metalloproteinase-generated neoepitope of CRP can identify knee and multi-joint inflammation in osteoarthritis |
title_fullStr | A matrix metalloproteinase-generated neoepitope of CRP can identify knee and multi-joint inflammation in osteoarthritis |
title_full_unstemmed | A matrix metalloproteinase-generated neoepitope of CRP can identify knee and multi-joint inflammation in osteoarthritis |
title_short | A matrix metalloproteinase-generated neoepitope of CRP can identify knee and multi-joint inflammation in osteoarthritis |
title_sort | matrix metalloproteinase-generated neoepitope of crp can identify knee and multi-joint inflammation in osteoarthritis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407005/ https://www.ncbi.nlm.nih.gov/pubmed/34465395 http://dx.doi.org/10.1186/s13075-021-02610-y |
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