文献类型：期刊文献

英文题名：A Translational Study of TNF-Alpha Antagonists as an Adjunctive Therapy for Preventing Hemophilic Arthropathy

作者：Zhang, Feixu[1,2];Xu, Mengyang[3];Yang, Qin[3];Hua, Baolai[3];Xia, Binglan[3];Lin, Zhenyang[2];Xiao, Xiao[2];Monahan, Paul E.[4,5,6];Sun, Junjiang[4,7]

机构：[1]East China Univ Sci & Technol, Sch Bioengn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China;[3]Yangzhou Univ, Dept Hematol, Clin Med Coll, Yangzhou 225001, Jiangsu, Peoples R China;[4]Univ N Carolina, Gene Therapy Ctr, Chapel Hill, NC 27599 USA;[5]Univ N Carolina, Harold R Roberts Comprehens Hemophilia Diag & Tre, Chapel Hill, NC 27599 USA;[6]Spark Therapeut, 3737 Market St, Philadelphia, PA 19104 USA;[7]Univ N Carolina, Eshelman Sch Pharm, Div Mol Pharmaceut, Chapel Hill, NC 27599 USA

年份：2020

卷号：9

期号：1

外文期刊名：JOURNAL OF CLINICAL MEDICINE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000515388400075)】；

基金：B.H. is the recipient of a grant from Beijing Municipal Natural Science Foundation (No. 7162151). The work was supported in part by a grant funding from Novo Nordisk Hemophilia Research Fund (NNHRF) China, an unrestricted grant from Novo Nordisk; Fundamental Research Funds for the Central Universities and National Natural Science Foundation (#81970171). J.S. received a research grant from Asklepios BioPharmaceutical during the preparation of the manuscript.

语种：英文

外文关键词：hemophilia; hemarthrosis; hemophilic arthropathy; TNF alpha; anti-TNF alpha

摘要：Repeated intra-articular hemorrhages lead to hemophilic arthropathy in severe hemophilia. Inflammation and pro-inflammatory cytokines (e.g., tumor necrosis factor alpha (TNF alpha)) might be involved in this pathogenesis. We hypothesized that anti-TNF alpha may provide adjuvant protection for hemophilic arthropathy management. We measured TNF alpha 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 alpha was initiated either from day (D)7 after one hemarthrosis episode or D21 after three hemarthroses episodes (n >= 7/treatment group). In patients with hemophilic arthropathy (16 patients with 17 affected joints), a single dose of anti-TNF alpha was administered intra-articularly. Efficacy, characterized by synovial membrane thickness and vascularity, was determined. Elevated TNF alpha 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 +/- 1.6). Factor IX (FIX) replacement alone partially improved the pathological changes (Synovitis score of 4.2 +/- 0.8). However, anti-TNF alpha treatment initiated at D7, not D21, significantly provided protection (Synovitis score of 1.8 +/- 0.9 vs. 3.9 +/- 0.3). In patients with hemophilic arthropathy, intra-articular anti-TNF alpha significantly decreased synovial thickness and vascularity during the observed period from D7 to D30. Collectively, this preliminary study seems to indicate that TNF alpha may be associated with the pathogenicity of hemophilic arthropathy and anti-TNF alpha could provide adjuvant protection against hemophilic arthropathy. Further studies are required to confirm the preliminary results shown in this study.