CD30-targeted therapy induces apoptosis of inflammatory cytokine-stimulated synovial fibroblasts and ameliorates collagen antibody-induced arthritis in mice
CD30-targeted therapy induces apoptosis of inflammatory cytokine-stimulated synovial fibroblasts and ameliorates collagen antibody-induced arthritis in mice
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CD30 靶向治疗可诱导炎症细胞因子刺激的滑膜成纤维细胞凋亡并改善胶原抗体诱导的小鼠关节炎
DOI：
10.1007/s00011-021-01537-z
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发表时间：
2022
影响因子：
6.7
通讯作者：
Ozaki T.
中科院分区：
文献类型：
--
作者：
Matsuhashi M;Nishida K;Sakamoto M;Gion Y;Yoshida A;Katsuyama T;Nakahara R;Nasu Y;Matsumoto Y;Sato Y;Ozaki T.
有研究表明，类风湿关节炎（RA）患者血清和关节液中可溶性CD 30水平显著升高。本研究旨在探讨CD 30是否可以作为治疗RA的靶点。方法采用免疫组化和免疫荧光双标法检测RA和骨关节炎（OA）滑膜组织中CD 30的表达和定位。应用聚合酶链反应（PCR）和流式细胞术检测RA患者成纤维样滑膜细胞（FLS）在TNFα和IL-1β刺激前后CD 30表达的变化。采用DBA/1小鼠建立胶原抗体诱导的关节炎（CAIA）模型，通过临床评分、组织学检查及血清SAA、IL-6和TNFα水平检测，观察维布妥昔单抗（BV）对CAIA的治疗作用。双重免疫荧光显示，CD 30与CD 20或CD 90的共定位率较低，但CD 30和CD 138的共定位率较高。CD 30 mRNA表达上调11.7倍，在FLS刺激后的炎性细胞因子。两种BV治疗后CAIA小鼠的临床评分均显著降低，但仅高剂量BV（70 mg/kg）治疗后CAIA小鼠的组织学评分显著降低。大剂量BV（70 mg/kg）对CAIA小鼠的炎症和关节破坏有明显的治疗作用，而小剂量BV（30 mg/kg）治疗效果不明显。
ObjectiveIt has been reported that levels of soluble CD30 in serum and joint fluid are significantly elevated in patients with rheumatoid arthritis (RA). This study aimed to investigate whether CD30 could be a therapeutic target for RA.MethodsThe expression and localization of CD30 were examined by immunohistochemical and double immunofluorescence staining on synovial tissue samples obtained from patients with RA or osteoarthritis (OA) during surgery. Changes in CD30 expression of fibroblast-like synoviocytes (FLS) from RA patients with or without TNFα and IL-1β stimulation were examined by the polymerase chain reaction (PCR) and flow cytometry. Collagen antibody-induced arthritis (CAIA) was created in DBA/1 mice, and the therapeutic effect of brentuximab vedotin (BV) was examined by clinical score, histological findings and measurement of serum levels of SAA, IL-6, and TNFα.ResultsCD30 expression was significantly higher in samples from patients with RA than from those with OA. Double immunofluorescence showed a low rate of co-localization of CD30 with CD20 or CD90, but a high rate of co-localization of CD30 and CD138. CD30 mRNA expression was upregulated 11.7-fold in FLS following stimulation by inflammatory cytokines. The clinical scores of CAIA mice were significantly lower following both BV treatments, however, the histological scores of CAIA mice were significantly lower only following treatment with high dose BV (70 mg/kg).ConclusionsCD30 was expressed on immunocompetent cells in synovial tissue from RA patients and in cytokine-stimulated FLS in vitro. High dose BV (70 mg/kg) showed significant therapeutic effects in ameliorating inflammation and joint destruction in CAIA mice, but low dose BV (30 mg/kg) was insufficient.
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影响因子：
--
作者：
Myasoedova, Elena;Crowson, Cynthia S.;Kremers, Hilal Maradit;Therneau, Terry M.;Gabriel, Sherine E.
通讯作者：
Gabriel, Sherine E.
影响因子：
4.6
作者：
R. Gerli;C. Muscat;O. Bistoni;B. Falini;C. Tomassini;E. Agea;R. Tognellini;P. Biagini;A. Bertotto
通讯作者：
R. Gerli;C. Muscat;O. Bistoni;B. Falini;C. Tomassini;E. Agea;R. Tognellini;P. Biagini;A. Bertotto
在类风湿性关节炎中，可溶性CD30配体以高水平存在并诱导CD30(+)T细胞凋亡。
影响因子：
4.4
作者：
E. Tinazzi;A. Barbieri;A. Rigo;Giuseppe Patuzzo;R. Beri;R. Gerli;Giuseppe Argentino;A. Puccetti;C. Lunardi
通讯作者：
C. Lunardi
影响因子：
4.4
作者：
Hye-Jung Kim;V. Krenn;G. Steinhauser;C. Berek
通讯作者：
Hye-Jung Kim;V. Krenn;G. Steinhauser;C. Berek
影响因子：
4.4
作者：
Sun, Xun;Yamada, Hisakata;Yoshikai, Yasunobu
通讯作者：
Yoshikai, Yasunobu