The story of complement factor I
The story of complement factor I
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DOI：
10.1016/j.imbio.2019.05.003
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发表时间：
2019-07-01
期刊：
影响因子：
2.8
通讯作者：
Lachmann, Peter J.
中科院分区：
文献类型：
--
作者：
Lachmann, Peter J.
因子 I 于 1966 年首次被发现。随着 1967 年对波士顿最初的因子 I 缺乏患者的描述，其重要性变得显而易见。该患者表现出过度活跃的替代补体途径，导致由于持续补体消耗而导致继发性补体缺乏。在这些发现的基础上，研究人员制定了替代途径的机制。 1975 年，人们惊奇地发现血浆中因子 I 的水平升高会下调旁路途径。将这一发现应用于临床的尝试经历了漫长而令人沮丧的历史，直到 2019 年，牛津大学的罗伯特·麦克拉伦教授爵士才用基因治疗载体治疗了第一位患者，以治疗年龄相关性黄斑变性。本综述遵循补体因子 I 从最初观察到临床应用的漫长而曲折的过程。
Factor I was first discovered in 1966. Its importance became apparent with the description of the original Factor I deficient patient in Boston in 1967. This patient presented with a hyperactive alternative complement pathway resulting in secondary complement deficiency due to continuous complement consumption. On the basis of these findings, the mechanism of the alternative pathway was worked out. In 1975, the surprise finding was made that elevating levels of Factor I in plasma down-regulated the alternative pathway. Attempts to exploit this finding for clinical use had a long and frustrating history and it was not until 2019 that the first patient was treated with the gene therapy vector for age related macular degeneration by Professor Sir Robert MacLaren in Oxford. This review follows the long and contorted course from initial observations to clinical use of complement Factor I.