Molecular Analysis of the Kidney From a Patient With COVID-19-Associated Collapsing Glomerulopathy.
Molecular Analysis of the Kidney From a Patient With COVID-19-Associated Collapsing Glomerulopathy.
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DOI：
10.1016/j.xkme.2021.02.012
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发表时间：
2021-07
期刊：
影响因子：
3.9
通讯作者：
Campbell KN
中科院分区：
文献类型：
--
作者：
Meliambro K;Li X;Salem F;Yi Z;Sun Z;Chan L;Chung M;Chancay J;Vy HMT;Nadkarni G;Wong JS;Fu J;Lee K;Zhang W;He JC;Campbell KN
最近的病例报告表明，2019年冠状病毒病（COVID-19）与具有载脂蛋白L1基因（APOL 1）风险等位基因的非洲裔美国人的肾小球疾病有关;然而，尚不清楚疾病发病机制是否与HIV相关肾病相似。对一名患有COVID-19相关塌陷性肾小球病和APOL 1风险等位基因（G1/G1）的患者的肾活检标本进行RNA测序分析，结果显示，与从GTEx（基因型-组织表达）门户网站下载的12份对照肾脏样本相比，APOL 1和血管紧张素转换酶2（ACE 2）信使RNA转录物水平相似。COVID-19相关塌陷性肾小球病肾脏样本的全基因组测序鉴定出4种indel基因变体，其中3种在慢性肾脏疾病和/或局灶节段性肾小球硬化症方面的意义未知。肾脏的分子谱显示了COVID-19相关细胞损伤途径的激活，如炎症和凝血。严重急性呼吸综合征冠状病毒2型直接感染肾细胞的证据缺乏，这与最近几项研究的结果一致。有趣的是，肾活检切片的免疫染色显示，与对照肾组织相比，COVID-19相关的塌陷性肾小球病和HIV相关肾病中磷酸化STAT 3（信号转导和转录激活因子3）的表达增加。重要的是，白细胞介素6诱导的STAT 3激活可能是驱动COVID-19相关急性肾损伤的靶向机制。
Recent case reports suggest that coronavirus disease 2019 (COVID-19) is associated with collapsing glomerulopathy in African Americans with apolipoprotein L1 gene (APOL1) risk alleles; however, it is unclear whether disease pathogenesis is similar to HIV-associated nephropathy. RNA sequencing analysis of a kidney biopsy specimen from a patient with COVID-19–associated collapsing glomerulopathy and APOL1 risk alleles (G1/G1) revealed similar levels of APOL1 and angiotensin-converting enzyme 2 (ACE2) messenger RNA transcripts as compared with 12 control kidney samples downloaded from the GTEx (Genotype-Tissue Expression) Portal. Whole-genome sequencing of the COVID-19–associated collapsing glomerulopathy kidney sample identified 4 indel gene variants, 3 of which are of unknown significance with respect to chronic kidney disease and/or focal segmental glomerulosclerosis. Molecular profiling of the kidney demonstrated activation of COVID-19–associated cell injury pathways such as inflammation and coagulation. Evidence for direct severe acute respiratory syndrome coronavirus 2 infection of kidney cells was lacking, which is consistent with the findings of several recent studies. Interestingly, immunostaining of kidney biopsy sections revealed increased expression of phospho-STAT3 (signal transducer and activator of transcription 3) in both COVID-19–associated collapsing glomerulopathy and HIV-associated nephropathy as compared with control kidney tissue. Importantly, interleukin 6–induced activation of STAT3 may be a targetable mechanism driving COVID-19–associated acute kidney injury.
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