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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 (<jats:italic>n<\/jats:italic>=25), and CD163 in serum (<jats:italic>n<\/jats:italic>=25) and synovial fluid (<jats:italic>n<\/jats:italic>=18).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>BMI was associated with CRP (<jats:italic>p<\/jats:italic>=0.001), but not CRPM (<jats:italic>p<\/jats:italic>=0.753). Adjusting for BMI, CRP was associated with radiographic knee osteophyte score (<jats:italic>p<\/jats:italic>=0.002), while CRPM was associated with synovitis of the knee (<jats:italic>p<\/jats:italic>=0.017), synovitis of multiple joints (<jats:italic>p<\/jats:italic>=0.008), and macrophage marker CD163 in serum (<jats:italic>p<\/jats:italic>=0.009) and synovial fluid (<jats:italic>p<\/jats:italic>=0.03). CRP correlated with MMP-generated neoepitope of type I collagen in serum (<jats:italic>p<\/jats:italic>=0.045), and CRPM correlated with MMP-generated neoepitope of type III collagen in serum (<jats:italic>p<\/jats:italic>&lt;0.0001). No biomarkers correlated with age, knee pain, or WOMAC pain.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>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.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13075-021-02610-y","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T05:02:47Z","timestamp":1630386167000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["A matrix metalloproteinase-generated neoepitope of CRP can identify knee and multi-joint inflammation in osteoarthritis"],"prefix":"10.1186","volume":"23","author":[{"suffix":"Jr","given":"Louie C.","family":"Alexander","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant","family":"McHorse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet L.","family":"Huebner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Christine","family":"Bay-Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten A.","family":"Karsdal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8173-8258","authenticated-orcid":false,"given":"Virginia B.","family":"Kraus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,31]]},"reference":[{"issue":"5","key":"2610_CR1","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1097\/BOR.0b013e328349c2b1","volume":"23","author":"MB Goldring","year":"2011","unstructured":"Goldring MB, Otero M. 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Sci Rep. 2020;10(1):10868. https:\/\/doi.org\/10.1038\/s41598-020-67730-y.","journal-title":"Sci Rep."}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-021-02610-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13075-021-02610-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-021-02610-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T05:03:37Z","timestamp":1630386217000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/s13075-021-02610-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,31]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2610"],"URL":"https:\/\/doi.org\/10.1186\/s13075-021-02610-y","relation":{},"ISSN":["1478-6362"],"issn-type":[{"value":"1478-6362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,31]]},"assertion":[{"value":"15 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study is a secondary analysis of samples derived from a previously reported pilot trial (NCT01237405). All procedures were conducted according to Declaration of Helsinki principles and approved by the Institutional Review Board of Duke University Medical Center.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Dr. Anne Bay-Jensen and Dr. Morten Karsdal are employees and shareholders of Nordic Biosciences. No other authors have any conflicts related to commercial interests in terms of stock, ownership, or honoraria.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"226"}}