Mode of action of abatacept in rheumatoid arthritis patients having failed tumour necrosis factor blockade: a histological, gene expression and dynamic magnetic resonance imaging pilot study.
Mode of action of abatacept in rheumatoid arthritis patients having failed tumour necrosis factor blockade: a histological, gene expression and dynamic magnetic resonance imaging pilot study.
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DOI：
10.1136/ard.2008.091876
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发表时间：
2009-07
影响因子：
27.4
通讯作者：
Emery P
中科院分区：
文献类型：
--
作者：
Buch MH;Boyle DL;Rosengren S;Saleem B;Reece RJ;Rhodes LA;Radjenovic A;English A;Tang H;Vratsanos G;O'Connor P;Firestein GS;Emery P
阿巴西普是目前唯一被批准用于治疗类风湿性关节炎（RA）的药物，其靶向完全T细胞活化所需的共刺激信号。尚未对其对滑膜（病理学的主要部位）的影响进行研究。本研究的目的是确定阿巴西普对RA患者的滑膜作用，以及对肿瘤坏死因子α（TNFα）阻断治疗的反应不足。这第一个机制研究纳入了治疗前和治疗后16周的动态对比增强（DCE）磁共振成像（MRI）和关节镜获得的滑膜活检，为免疫组织化学和定量实时PCR分析提供组织。研究了16例患者（13例女性）;所有患者既往均接受过TNFα阻断治疗失败。15名患者完成了研究。滑膜活检显示细胞含量略有减少，仅B细胞有显著性。定量PCR显示大多数炎症基因的表达降低（Wald统计量p<0.01，表明治疗效果显著），特别是IFNγ的表达降低了-52%（95%CI-73至15，p<0.05）;这与MRI改善密切相关。此外，还观察到骨保护素和核因子κ B受体激活剂水平的有利变化。DCE-MRI显示MRI参数降低15-40%。这些结果表明阿巴西普降低滑膜的炎症状态而不破坏细胞稳态。基因表达的减少对骨有积极影响，并为最近证实的阿巴西普治疗RA患者的放射学改善提供了依据。
Abatacept is the only agent currently approved to treat rheumatoid arthritis (RA) that targets the co-stimulatory signal required for full T-cell activation. No studies have been conducted on its effect on the synovium, the primary site of pathology. The aim of this study was to determine the synovial effect of abatacept in patients with RA and an inadequate response to tumour necrosis factor alpha (TNFα) blocking therapy. This first mechanistic study incorporated both dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and arthroscopy-acquired synovial biopsies before and 16 weeks after therapy, providing tissue for immunohistochemistry and quantitative real-time PCR analyses. Sixteen patients (13 women) were studied; all had previously failed TNFα-blocking therapy. Fifteen patients completed the study. Synovial biopsies showed a small reduction in cellular content, which was significant only for B cells. The quantitative PCR showed a reduction in expression for most inflammatory genes (Wald statistic of p<0.01 indicating a significant treatment effect), with particular reduction in IFNγ of −52% (95% CI −73 to −15, p<0.05); this correlated well with MRI improvements. In addition, favourable changes in the osteoprotegerin and receptor activator of nuclear factor kappa B levels were noted. DCE–MRI showed a reduction of 15–40% in MRI parameters. These results indicate that abatacept reduces the inflammatory status of the synovium without disrupting cellular homeostasis. The reductions in gene expression influence bone positively and suggest a basis for the recently demonstrated radiological improvements that have been seen with abatacept treatment in patients with RA.
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B7-1和B7-2共刺激配体的比较分析：表达和功能。
DOI：
10.1084/jem.180.2.631
发表时间：
1994-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hathcock KS;Laszlo G;Pucillo C;Linsley P;Hodes RJ
通讯作者：
Hodes RJ
影响因子：
--
作者：
Gerlag, DM;Haringman, JJ;Tak, PP
通讯作者：
Tak, PP
影响因子：
--
作者：
Tak, PP;Taylor, PC;Maini, RN
通讯作者：
Maini, RN
影响因子：
27.4
作者：
Veale, DJ;Reece, RJ;Emery, P
通讯作者：
Emery, P
影响因子：
--
作者：
Cohen, Stanley B.;Emery, Paul;Totoritis, Mark C.
通讯作者：
Totoritis, Mark C.