Endothelial Cell-Activating Antibodies in COVID-19.
Endothelial Cell-Activating Antibodies in COVID-19.
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DOI：
10.1002/art.42094
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发表时间：
2022-07
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虽然内皮功能障碍与 COVID-19 广泛的血栓炎症并发症有关，但内皮病的上游介质在很大程度上仍然未知。本研究旨在确定导致 COVID-19 中内皮细胞活化和功能障碍的循环因素。在 244 名因 COVID-19 住院的患者的血清或血浆以及 100 名非 COVID-19 相关脓毒症患者的血浆存在的情况下培养人内皮细胞。使用细胞内酶联免疫吸附测定对细胞粘附分子（E-选择素、血管细胞粘附分子 1 和细胞间粘附分子 1 [ICAM-1]）进行定量。来自 COVID-19 患者的血清和血浆增加了细胞粘附分子的表面表达。此外，患者血清中可溶性 ICAM-1 和 E-选择素的水平升高，并且与疾病严重程度相关。循环抗磷脂抗体的存在是 COVID-19 血清激活内皮细胞能力的有力标志。抗磷脂抗体阳性血清中总 IgG 的消耗显着降低了细胞粘附分子的上调。相反，用患者 IgG 补充对照血清足以触发内皮激活。这些数据首次表明，一些 COVID-19 患者可能具有导致内皮病的多种抗体，为重症 COVID-19 中自身抗体的血栓炎症作用提供了重要背景。
While endothelial dysfunction has been implicated in the widespread thromboinflammatory complications of COVID‐19, the upstream mediators of endotheliopathy remain, for the most part, unknown. This study was undertaken to identify circulating factors contributing to endothelial cell activation and dysfunction in COVID‐19. Human endothelial cells were cultured in the presence of serum or plasma from 244 patients hospitalized with COVID‐19 and plasma from 100 patients with non–COVID‐19–related sepsis. Cell adhesion molecules (E‐selectin, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 [ICAM‐1]) were quantified using in‐cell enzyme‐linked immunosorbent assay. Serum and plasma from COVID‐19 patients increased surface expression of cell adhesion molecules. Furthermore, levels of soluble ICAM‐1 and E‐selectin were elevated in patient serum and correlated with disease severity. The presence of circulating antiphospholipid antibodies was a strong marker of the ability of COVID‐19 serum to activate endothelium. Depletion of total IgG from antiphospholipid antibody–positive serum markedly reduced the up‐regulation of cell adhesion molecules. Conversely, supplementation of control serum with patient IgG was sufficient to trigger endothelial activation. These data are the first to indicate that some COVID‐19 patients have potentially diverse antibodies that drive endotheliopathy, providing important context regarding thromboinflammatory effects of autoantibodies in severe COVID‐19.