狼和COVID-19之间中性粒细胞转录组的大量重叠,狼特异性基因表达有限
Rayan Najjar1, Noga Rogel1, Jose Mario Bello Pineda1
1Department of Medicine, University of Washington, Seattle, Washington, USA.
Lupus science & medicine
|February 1, 2024
概括
通过比较系统性红斑狼 (SLE) 和COVID-19患者中性粒细胞的基因表达,发现它们与病毒感染有相似之处. 独特的SLE反应涉及RNA编辑酶,表明不同的疾病机制.
科学领域:
- 免疫学和分子生物学
- 基因组学和转录基因组学
- 类风湿病学 类风湿病学
背景情况:
- 系统性红斑狼 (SLE) 的病因尚不清楚.
- 中性粒细胞在SLE的发病过程中起着重要作用.
- 严重急性呼吸系统综合征-冠状病毒-2 (SARS-CoV-2) 感染 (COVID-19) 呈现出一个明确的抗原刺激,具有显著的I型干扰素反应.
研究的目的:
- 在SLE患者中研究中性粒细胞的基因表达特征.
- 将SLE中性粒细胞基因表达与SARS-CoV-2感染患者中性粒细胞的基因表达进行比较.
- 确定SLE和COVID-19之间的共同和独特的转录变化,重点关注差异性基因调节.
主要方法:
- 在SLE患者 (n=15) 和健康对照组 (n=12) 的中性粒细胞上进行了RNA测序.
- 对SLE和COVID-19中性粒细胞数据集进行了差异性基因表达和途径分析.
- 对比分析确定了常见和独特的转录变化,强调了对立调节的基因.
主要成果:
- 与健康对照组相比,SLE中性粒细胞中发现了372个差异表达的基因 (≥2倍,p<0.05).
- 其中181个基因显示出与SARS-CoV-2感染个体中观察到的转录变异一致的变化.
- 118个基因表现出SLE特有的统计学上显著的变化,其中28个基因在两种疾病之间以相反的方向调节.
结论:
- SLE和COVID-19之间中性粒细胞反应的显著重叠表明,SLE的病因可能与病毒感染功能相似,导致可比的免疫激活和I型干扰素反应.
- 反调节的基因突出显示了SLE特有的反应,包括涉及铁蛋白硫转移酶-1和APOBEC家族核酸脱氨酶的反应.
- 这些独特的SLE反应涉及RNA和DNA编辑,以及其他RNA修饰酶,表明SLE发病过程中存在不同的分子机制.
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