从猪移植到人移植后的免疫反应:多模式表型化研究
Alexandre Loupy1, Valentin Goutaudier1, Alessia Giarraputo2
1Université Paris Cité, INSERM U970 PARCC, Paris Institute for Transplantation and Organ Regeneration, Paris, France; Department of Kidney Transplantation, Necker Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.
Lancet (London, England)
|August 20, 2023
概括
猪移植显示出抗体中介排斥的早期迹象,尽管最初的成功. 这种免疫反应涉及先天免疫细胞和补体激活,突出了改善异种移植存活率的目标.
科学领域:
- 移植免疫学
- 异种移植
- 基因组工程
背景情况:
- 跨物种的免疫不相容性历来阻碍了猪对人类的异种移植.
- 猪基因组工程的近期进展使初步成功的异种移植实验成为可能.
- 猪移植后对人类接受者的早期免疫反应尚不清楚.
研究的目的:
- 准确地描述猪对人类移植的早期免疫反应.
- 使用多模式深度表型方法分析异种移植免疫反应.
- 确定减轻异种移植排斥的潜在治疗点.
主要方法:
- 在已故人类接受者身上进行了两次猪移植的完整表型鉴定.
- 采用多模式策略,包括形态评估,免疫类型,基因表达概况和数字空间概况.
- 使用的对照组:植入前异位移植,野生猪自移植和非移植的猪,有/没有缺血再输血.
主要成果:
- 异位移植患者表现出抗体中介排斥的早期迹象,其特征是微血管炎症,免疫沉积和内皮细胞激活.
- 毛细血管炎症涉及血管内天生的免疫细胞 (CD68+,CD15+,NKp46+).
- 观察到与幽默反应,单细胞/巨细胞激活,NK细胞负担,内皮激活,补体激活和T细胞发育相关的基因表达增加.
结论:
- 尽管短期的结果是有利的,但在猪对人类的移植中可能会出现抗体介导的排斥.
- 这些发现表明在体内免疫反应途径中存在特定的治疗点.
- 这些目标有可能提高猪对人类移植的长期成功率.
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