The therapeutic potential of costimulatory blockade with CTLA4Ig in rheumatoid arthritis
The therapeutic potential of costimulatory blockade with CTLA4Ig in rheumatoid arthritis
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DOI：
10.1517/13543784.12.4.673
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发表时间：
2003-04-01
影响因子：
6.1
通讯作者：
Emery, P
中科院分区：
文献类型：
--
作者：
Emery, P
类风湿性关节炎（RA）是一种慢性、全身性炎症性疾病，其特征是关节炎症和破坏。关于活化 T 细胞在 RA 中的重要性和确切作用存在争议。 CTLA4Ig 是一种可溶性融合蛋白（细胞毒性 T 淋巴细胞相关抗原 4 与人 IgG1 重链恒定区融合），是称为共刺激阻滞剂的新型药物中的第一种药物。通过阻断最佳 T 细胞激活所需的第二个信号，CTLA4Ig 在多种自发性和诱导性自身免疫动物模型中显示出功效。 RA 的 II 期临床研究表明 CTLA4Ig 有效且安全性可接受。这些结果表明，活化的 T 细胞可能在 RA 发病机制中发挥重要作用，共刺激阻断可能是治疗这种疾病的一种新方法。
Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disorder characterised by joint inflammation and destruction. Controversy exists regarding the significance and exact role of activated T cells in RA. CTLA4Ig is a soluble fusion protein (cytotoxic T lymphocyte-associated antigen 4 fused to the heavy chain constant region of human IgG1), which represents the first in a new class of agents called costimulation blockers. By blocking the second signal required for optimal T-cell activation, CTLA4Ig has demonstrated efficacy in a variety of spontaneous and induced animal models of autoimmunity. A Phase II clinical study in RA showed CTLA4Ig was efficacious with an acceptable safety profile. These results suggest that activated T cells may be important in RA pathogenesis and that costimulation blockade may be a novel therapeutic approach for this disorder.