Docked severe acute respiratory syndrome coronavirus 2 proteins within the cutaneous and subcutaneous microvasculature and their role in the pathogenesis of severe coronavirus disease 2019.
Docked severe acute respiratory syndrome coronavirus 2 proteins within the cutaneous and subcutaneous microvasculature and their role in the pathogenesis of severe coronavirus disease 2019.
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DOI：
10.1016/j.humpath.2020.10.002
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发表时间：
2020-12
期刊：
影响因子：
3.3
通讯作者：
Nuovo GJ
中科院分区：
文献类型：
--
作者：
Magro CM;Mulvey JJ;Laurence J;Seshan S;Crowson AN;Dannenberg AJ;Salvatore S;Harp J;Nuovo GJ
本研究的目的是检查 23 名 2019 年冠状病毒病 (COVID-19)（病情最严重）患者的三角肌皮肤活检中的血管补体沉积情况，并将其与严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 病毒 RNA 和蛋白质定位以及 ACE2 表达相关联。三角肌皮肤微血管补体筛查已应用于患有各种全身补体介导的微血管综合征的患者，最好的例子是非典型溶血性尿毒症综合征。 23 例中有 21 例发现补体成分大量微血管沉积。两名没有显着补体沉积的患者包括一名中度疾病患者和一名重度患者，尽管使用了一天呼吸机，但三天后就出院了。鉴定出的主要微血管补体免疫反应物是末端膜溶解攻击复合物 C5b-9。微血管补体沉积与 SARS-CoV-2 病毒蛋白（包括内皮细胞中的刺突糖蛋白）以及病变和非病变皮肤中的病毒受体 ACE2 强烈共定位；病毒RNA不明显。微血管 SARS-CoV-2 病毒蛋白、补体和 ACE2 表达在皮下脂肪中最为明显。尽管来自患有 COVID-19 的重症患者的样本来自大体正常的皮肤，但光镜下局灶性微血管异常是明显的，包括内皮细胞剥脱、基底膜区重复和小血栓。结论是，补体激活在严重正常的皮肤中很常见，特别是在皮下脂肪中，这可能在严重的 COVID-19 患者中提供严重疾病和肥胖之间的联系，并且与 ACE2 受体和病毒衣壳蛋白（不含病毒 RNA）的强烈共定位表明循环病毒蛋白（即假病毒体）可能会停靠在这些微血管的内皮上并诱导补体激活。
The purpose of this study was to examine the deltoid skin biopsy in twenty-three patients with coronavirus disease 2019 (COVID-19), most severely ill, for vascular complement deposition and correlate this with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA and protein localization and ACE2 expression. Deltoid skin microvascular complement screening has been applied to patients with various systemic complement-mediated microvascular syndromes, best exemplified by atypical hemolytic uremic syndrome. In 21 of 23 cases, substantial microvascular deposition of complement components was identified. The two patients without significant complement deposition included one patient with moderate disease and a severely ill patient who although on a ventilator for a day was discharged after 3 days. The dominant microvascular complement immunoreactant identified was the terminal membranolytic attack complex C5b-9. Microvascular complement deposition strongly colocalized in situ with the SARS-CoV-2 viral proteins including spike glycoproteins in the endothelial cells as well as the viral receptor ACE2 in lesional and nonlesional skin; viral RNA was not evident. Microvascular SARS-CoV-2 viral protein, complement, and ACE2 expression was most conspicuous in the subcutaneous fat. Although the samples from severely ill patients with COVID-19 were from grossly normal skin, light microscopically focal microvascular abnormalities were evident that included endothelial cell denudement, basement membrane zone reduplication, and small thrombi. It is concluded that complement activation is common in grossly normal skin, especially in the subcutaneous fat which may provide a link between severe disease and obesity, in people with severe COVID-19, and the strong colocalization with the ACE2 receptor and viral capsid proteins without viral RNA suggests that circulating viral proteins (ie, pseudovirions) may dock onto the endothelial of these microvessels and induce complement activation.
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DOI：
10.4049/jimmunol.0903678
发表时间：
2010-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Amara U;Flierl MA;Rittirsch D;Klos A;Chen H;Acker B;Brückner UB;Nilsson B;Gebhard F;Lambris JD;Huber-Lang M
通讯作者：
Huber-Lang M
DOI：
10.1161/atvbaha.110.218123
发表时间：
2011-01-01
影响因子：
8.7
作者：
Dignat-George, Francoise;Boulanger, Chantal M.
通讯作者：
Boulanger, Chantal M.
影响因子：
10.3
作者：
Magro, C. M.;Mulvey, J. J.;Nuovo, G.
通讯作者：
Nuovo, G.
影响因子：
1.1
作者：
Magro, Cynthia M.;Momtahen, Shabnam;Laurence, Jeffrey C.
通讯作者：
Laurence, Jeffrey C.
影响因子：
2
作者：
Chu AJ
通讯作者：
Chu AJ