{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T13:56:08Z","timestamp":1758635768884},"reference-count":37,"publisher":"Wiley","issue":"s4","license":[{"start":{"date-parts":[[2014,4,25]],"date-time":"2014-04-25T00:00:00Z","timestamp":1398384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>One of the main complications of haemophilia A is haemophilic arthropathy (<jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>), a debilitating disease with a significant negative impact on motility and quality of life. Despite major advances in the treatment of haemophilia A, many patients still suffer from <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>. We wish to develop new treatments for <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>, but must first better understand its causes. Our laboratory studies molecular scissors that release the pro\u2010inflammatory cytokine tumour necrosis factor alpha (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u03b1) from cells. <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u03b1 is considered the \u2018fire alarm\u2019 of the body \u2013 it helps to fight infections, but can also cause diseases such as inflammatory arthritis. We know that the molecular scissors, called <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u03b1 convertase (<jats:styled-content style=\"fixed-case\">TACE<\/jats:styled-content>), and its newly discovered regulator termed iRhom2 can be rapidly activated by small amounts of cytokines, growth factors, and pro\u2010inflammatory mediators present in the blood. We hypothesize that the rapid activation of <jats:styled-content style=\"fixed-case\">TACE<\/jats:styled-content> could help explain one of the unsolved mysteries regarding the development of <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>, which is how even small amounts of blood can provoke a persistent inflammatory response. We propose that once blood enters the joint, iRhom2 and TACE are activated to release <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u03b1 and that this could promote the development of HA in a similar manner to that in which it promotes rheumatoid arthritis (<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>). We are currently using immune cells stimulated with blood degradation products, and mouse models of <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>, to test this hypothesis. If successful, our study could provide the rationale for testing anti\u2010<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> antibodies, which are already used to treat <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>, for the treatment of <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>. In addition, they might uncover iRhom2 and TACE as attractive new candidate targets for the treatment of <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/hae.12416","type":"journal-article","created":{"date-parts":[[2014,4,25]],"date-time":"2014-04-25T09:03:49Z","timestamp":1398416629000},"page":"11-14","source":"Crossref","is-referenced-by-count":10,"title":["With blood in the joint \u2013 what happens next? Could activation of a pro\u2010inflammatory signalling axis leading to iRhom2\/TNF\u03b1\u2010convertase\u2010dependent release of TNF\u03b1 contribute to haemophilic arthropathy?"],"prefix":"10.1111","volume":"20","author":[{"given":"C.","family":"Haxaire","sequence":"first","affiliation":[{"name":"Arthritis &amp; Tissue Degeneration Program Hospital for Special Surgery at Weill Medical College of Cornell University New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. P.","family":"Blobel","sequence":"additional","affiliation":[{"name":"Arthritis &amp; Tissue Degeneration Program Hospital for Special Surgery at Weill Medical College of Cornell University New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,4,25]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.1994.tb00815.x"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.03962.x"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2012.02835.x"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2006.01208.x"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00014347"},{"key":"e_1_2_5_7_1","doi-asserted-by":"crossref","unstructured":"Manco\u2010JohnsonMM AbshireTC BrownDet\u00a0al.Initial results of a randomized prospective trial of prophylaxis to prevent joint disease 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