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ALDH4A1是一种由保护性抗体向的动脉样硬化自身抗原
Cristina Lorenzo1, Pilar Delgado1,2, Christian E Busse3
1B Lymphocyte Biology Lab, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Nature
|December 3, 2020
概括
研究人员确定了针对动脉样硬化的ALDH4A1的自身抗体. 这些抗体可以作为生物标志物,通过防止斑块形成,为心血管疾病 (CVD) 提供治疗潜力.
科学领域:
- 免疫学
- 心血管医学
- 蛋白质组学
背景情况:
- 心血管疾病 (CVD) 是全球主要的死亡原因,主要是心肌梗塞和中风.
- 动脉样硬化是一种炎症性疾病,是大多数心血管疾病的根源,并且可以长时间无症状.
- 自动抗体及其触发因子在动脉样硬化中的作用尚不清楚,这凸显出需要新的诊断和治疗策略.
研究的目的:
- 使用高通量单细胞分析研究动脉样硬化相关的抗体库.
- 在动脉样硬化中识别针对抗体的特定自身抗原.
- 评估已识别的自身抗体作为CVD的生物标志物和治疗剂的潜力.
主要方法:
- 从1700多个B细胞中对抗体基因测序的高通量单细胞分析.
- 深度蛋白质组学分析以确定扩展B细胞克隆的自身抗原标.
- 在Ldlr-/-小鼠体内进行抗体输注,以评估对斑块形成和脂质水平的影响.
主要成果:
- 在动脉样硬化的背景下,从体内扩张的B细胞克隆中鉴定出56个抗体.
- 其中三分之一的抗体对动脉样硬化斑块有反应性,表明与病变相关的各种自身抗原.
- ALDH4A1被确定为向抗原;它的循环水平在动脉样硬化中升高,而抗ALDH4A1抗体 (A12) 延迟了斑块的进展,并改善了小鼠的脂质概况.
结论:
- 动脉样硬化涉及针对各种斑块抗原的显著自身抗体反应,包括ALDH4A1.
- 由于分布变化和循环水平增加,ALDH4A1显示为动脉样硬化的生物标志物.
- 抗ALDH4A1抗体显示对动脉样硬化进展的保护作用,表明对心血管疾病的治疗潜力.
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