Casciola-Rosen Livia, Thiemann David R, Andrade Felipe, Trejo Zambrano Maria Isabel, Hooper Jody E, Leonard Elissa K, Spangler Jamie B, Cox Andrea L, Machamer Carolyn E, Sauer Lauren, Laeyendecker Oliver, Garibaldi Brian T, Ray Stuart C, Mecoli Christopher A, Christopher-Stine Lisa, Gutierrez-Alamillo Laura, Yang Qingyuan, Hines David, Clarke William A, Rothman Richard, Pekosz Andrew, Fenstermacher Katherine J, Wang Zitong, Zeger Scott L, Rosen Antony
Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Medicine, Divisioin of Cardiology, Jhohns Hopkins University School of Medicine, Baltimore, Maryland.
medRxiv. 2020 Oct 15:2020.10.13.20211664. doi: 10.1101/2020.10.13.20211664.
SARS-CoV-2 infection induces severe disease in a subpopulation of patients, but the underlying mechanisms remain unclear. We demonstrate robust IgM autoantibodies that recognize angiotensin converting enzyme-2 (ACE2) in 18/66 (27%) patients with severe COVID-19, which are rare (2/52; 3.8%) in hospitalized patients who are not ventilated. The antibodies do not undergo class-switching to IgG, suggesting a T-independent antibody response. Purified IgM from anti-ACE2 patients activates complement. Pathological analysis of lung obtained at autopsy shows endothelial cell staining for IgM in blood vessels in some patients. We propose that vascular endothelial ACE2 expression focuses the pathogenic effects of these autoantibodies on blood vessels, and contributes to the angiocentric pathology observed in some severe COVID-19 patients. These findings may have predictive and therapeutic implications.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染在部分患者中会引发重症疾病，但其潜在机制仍不清楚。我们发现，在18/66（27%）的重症2019冠状病毒病（COVID-19）患者体内存在能识别血管紧张素转换酶2（ACE2）的强效IgM自身抗体，而在未接受机械通气的住院患者中这种抗体很罕见（2/52；3.8%）。这些抗体不会发生类别转换为IgG，提示这是一种非T细胞依赖的抗体反应。从抗ACE2患者中纯化得到的IgM可激活补体。尸检获得的肺部病理分析显示，部分患者血管内的内皮细胞有IgM染色。我们提出，血管内皮ACE2的表达使这些自身抗体的致病作用集中于血管，并导致了部分重症COVID-19患者出现的血管中心性病理改变。这些发现可能具有预测和治疗意义。
