{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:25:11Z","timestamp":1783445111447,"version":"3.54.6"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,4,24]],"date-time":"2017-04-24T00:00:00Z","timestamp":1492992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Danish Research Foundation (\u2018Den Danske Forskningsfond\u2019)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Progressive arthropathy caused by recurrent joint bleeds is a severe complication in haemophilia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>We investigated whether biomarkers of cartilage and bone degradation, and inflammation were altered in haemophilia patients and whether these biomarkers could identify haemophilia patients with arthropathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serum from 35 haemophilia patients with varying degrees of arthropathy and 43 age\u2010 and gender\u2010matched control subjects were analysed. Biomarkers of cartilage degradation (C2M, <jats:styled-content style=\"fixed-case\">COMP<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> CTX<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> ADAMTS<\/jats:styled-content>5), cartilage formation (<jats:styled-content style=\"fixed-case\">PRO<\/jats:styled-content>\u2010C2), bone formation (<jats:styled-content style=\"fixed-case\">PINP<\/jats:styled-content>), bone resorption (<jats:styled-content style=\"fixed-case\">CTX<\/jats:styled-content>\u2010I) and inflammation (hs<jats:styled-content style=\"fixed-case\">CRP<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> CRPM<\/jats:styled-content>) were measured by <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content>. Arthropathy was assessed by radiological evaluation (Pettersson score) and physical examination (Gilbert score).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In patients with haemophilia, cartilage degradation, measured by C2M, <jats:styled-content style=\"fixed-case\">CTX<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">COMP<\/jats:styled-content>, was increased by 25% (<jats:italic>P<\/jats:italic> &lt; 0.05) compared with control subjects. Levels of the cartilage degradation enzyme, <jats:styled-content style=\"fixed-case\">ADAMTS<\/jats:styled-content>5, were 10% lower in haemophilia patients (<jats:italic>P<\/jats:italic> &lt; 0.05). Bone formation (<jats:styled-content style=\"fixed-case\">PINP<\/jats:styled-content>) was reduced by 25% (<jats:italic>P<\/jats:italic> &lt; 0.05) in haemophilia patients, whereas bone resorption (<jats:styled-content style=\"fixed-case\">CTX<\/jats:styled-content>\u2010I) was increased by 30% (<jats:italic>P<\/jats:italic> &lt; 0.001). Acute inflammation (hs<jats:styled-content style=\"fixed-case\">CRP<\/jats:styled-content>) was increased by 50% (<jats:italic>P<\/jats:italic> &lt; 0.01), whereas chronic inflammation (<jats:styled-content style=\"fixed-case\">CRPM<\/jats:styled-content>) was decreased by 25% (<jats:italic>P<\/jats:italic> &lt; 0.0001). The hs<jats:styled-content style=\"fixed-case\">CRP<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">CRPM<\/jats:styled-content> ratio was 60% higher (<jats:italic>P<\/jats:italic> &lt; 0.001) in haemophilia patients relative to control subjects. A biomarker panel combining C2M, <jats:styled-content style=\"fixed-case\">CRPM<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">ADAMTS<\/jats:styled-content>5 could distinguish haemophilia patients from control subjects with 85.3% accuracy (<jats:italic>P<\/jats:italic> &lt; 0.0001). We found no strong correlation between biomarkers and radiological and physical examination of the joint.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Biomarkers detect increased cartilage and bone degradation, and altered inflammatory activity in haemophilia patients with arthropathy. These biomarkers could potentially be used to identify patients with progressing joint disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.13196","type":"journal-article","created":{"date-parts":[[2017,4,25]],"date-time":"2017-04-25T02:03:07Z","timestamp":1493085787000},"source":"Crossref","is-referenced-by-count":26,"title":["Serological biomarkers detect active joint destruction and inflammation in patients with haemophilic arthropathy"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1712-0768","authenticated-orcid":false,"given":"B.","family":"Hua","sequence":"first","affiliation":[{"name":"Department of Hematology Chinese Academy of Medical Sciences (CAMS) &amp; Peking Union Medical College (PUMC) Peking Union Medical College Hospital (PUMCH) Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. H. 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