{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:24:38Z","timestamp":1790220278215,"version":"4.1.0"},"reference-count":48,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T00:00:00Z","timestamp":1577404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Repeated intra-articular hemorrhages lead to hemophilic arthropathy in severe hemophilia. Inflammation and pro-inflammatory cytokines (e.g., tumor necrosis factor alpha (TNF\u03b1)) might be involved in this pathogenesis. We hypothesized that anti-TNF\u03b1 may provide adjuvant protection for hemophilic arthropathy management. We measured TNF\u03b1 in synovial lavage from hemophilia mice subjected to hemarthrosis induction and synovial fluid from patients with hemophilic arthropathy (n = 5). In hemophilia mice, recurrent hemarthroses were induced, anti-TNF\u03b1 was initiated either from day (D)7 after one hemarthrosis episode or D21 after three hemarthroses episodes (n \u2265 7\/treatment group). In patients with hemophilic arthropathy (16 patients with 17 affected joints), a single dose of anti-TNF\u03b1 was administered intra-articularly. Efficacy, characterized by synovial membrane thickness and vascularity, was determined. Elevated TNF\u03b1 in synovial lavage was found in the hemophilia mice and patients with hemophilic arthropathy. Hemophilia mice subjected to three hemarthroses developed severe synovitis (Synovitis score of 6.0 \u00b1 1.6). Factor IX (FIX) replacement alone partially improved the pathological changes (Synovitis score of 4.2 \u00b1 0.8). However, anti-TNF\u03b1 treatment initiated at D7, not D21, significantly provided protection (Synovitis score of 1.8 \u00b1 0.9 vs. 3.9 \u00b1 0.3). In patients with hemophilic arthropathy, intra-articular anti-TNF\u03b1 significantly decreased synovial thickness and vascularity during the observed period from D7 to D30. Collectively, this preliminary study seems to indicate that TNF\u03b1 may be associated with the pathogenicity of hemophilic arthropathy and anti-TNF\u03b1 could provide adjuvant protection against hemophilic arthropathy. Further studies are required to confirm the preliminary results shown in this study.<\/jats:p>","DOI":"10.3390\/jcm9010075","type":"journal-article","created":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T11:42:47Z","timestamp":1577446967000},"page":"75","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A Translational Study of TNF-Alpha Antagonists as an Adjunctive Therapy for Preventing Hemophilic Arthropathy"],"prefix":"10.3390","volume":"9","author":[{"given":"Feixu","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Bioengineering, East China University of Science and Technology, Shanghai\u200e 200237, China"},{"name":"School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Hematology, Clinical Medical College, Yangzhou University, Yangzhou 225001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Clinical Medical College, Yangzhou University, Yangzhou 225001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baolai","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Hematology, Clinical Medical College, Yangzhou University, Yangzhou 225001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binglan","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Hematology, Clinical Medical College, Yangzhou University, Yangzhou 225001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyang","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Xiao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2110-0740","authenticated-orcid":false,"given":"Paul E.","family":"Monahan","sequence":"additional","affiliation":[{"name":"Gene Therapy Center, University of North Carolina, Chapel Hill, NC 27599, USA"},{"name":"Harold R. Roberts Comprehensive Hemophilia Diagnosis and Treatment Center, University of North Carolina, Chapel Hill, NC 27599, USA"},{"name":"Spark Therapeutics, 3737 Market Street, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7408-0731","authenticated-orcid":false,"given":"Junjiang","family":"Sun","sequence":"additional","affiliation":[{"name":"Gene Therapy Center, University of North Carolina, Chapel Hill, NC 27599, USA"},{"name":"Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1586\/ehm.12.27","article-title":"Management of joint bleeding in hemophilia","volume":"5","author":"Simpson","year":"2012","journal-title":"Expert Rev. 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