Pathogenic lipid-binding antiphospholipid antibodies are associated with severity of COVID-19.
Pathogenic lipid-binding antiphospholipid antibodies are associated with severity of COVID-19.
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DOI：
10.1111/jth.15455
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Lackner KJ
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文献类型：
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作者：
Hollerbach A;Müller-Calleja N;Pedrosa D;Canisius A;Sprinzl MF;Falter T;Rossmann H;Bodenstein M;Werner C;Sagoschen I;Münzel T;Schreiner O;Sivanathan V;Reuter M;Niermann J;Galle PR;Teyton L;Ruf W;Lackner KJ
冠状病毒病19（COVID-19）相关凝血病是疾病严重程度和预后不良的标志。这种血栓前综合征的主要表现微血管血栓形成、中风、静脉和肺血栓也可在严重和灾难性的抗磷脂综合征中观察到。抗磷脂抗体（aPL）在COVID-19患者中可检测到，但其与COVID-19临床病程的相关性尚未得到证实。分析住院COVID-19患者中脂质结合aPL的存在及其相关性。分析了来自一个中心的53名和121名因PCR证实的严重急性呼吸综合征-冠状病毒2型感染住院的患者的两个队列的aPL存在情况和COVID-19的临床严重程度。我们在此证明脂质结合aPL在COVID-19中很常见。患有脂质结合性aPL的COVID-19患者的C反应蛋白和D二聚体的中位浓度较高，并且更有可能出现严重的临床病程和致死性结局。从COVID-19患者中分离的脂质结合aPL靶向最近描述的溶血双磷脂酸（LBPA）与蛋白C受体（EPCR）的细胞表面复合物，以诱导单核细胞和内皮细胞中的促血栓形成和炎症反应。我们发现，产生IgG同种型的脂质反应性aPL的B1 a细胞在COVID-19患者的血液中循环。在体内，COVID-19 aPL在实验小鼠模型中加速血栓形成，这取决于最近描述的涉及EPCR-LBPA的信号通路。COVID-19患者迅速扩增B1 a细胞，分泌致病性脂质结合aPL，具有广泛的血栓形成和炎症效应。与炎症和凝血标志物、临床严重程度和死亡率的相关性表明aPL在COVID-19相关凝血病中的因果作用。
Coronavirus disease 19 (COVID‐19)–associated coagulopathy is a hallmark of disease severity and poor prognosis. The key manifestations of this prothrombotic syndrome—microvascular thrombosis, stroke, and venous and pulmonary clots—are also observed in severe and catastrophic antiphospholipid syndrome. Antiphospholipid antibodies (aPL) are detectable in COVID‐19 patients, but their association with the clinical course of COVID‐19 remains unproven. To analyze the presence and relevance of lipid‐binding aPL in hospitalized COVID‐19 patients. Two cohorts of 53 and 121 patients from a single center hospitalized for PCR‐proven severe acute respiratory syndrome–coronavirus 2 infection were analyzed for the presence of aPL and clinical severity of COVID‐19. We here demonstrate that lipid‐binding aPL are common in COVID‐19. COVID‐19 patients with lipid‐binding aPL have higher median concentrations of C‐reactive protein and D‐dimer, and are more likely to have a critical clinical course and fatal outcome. Lipid‐binding aPL isolated from COVID‐19 patients target the recently described cell surface complex of lysobisphosphatidic acid (LBPA) with the protein C receptor (EPCR) to induce prothrombotic and inflammatory responses in monocytes and endothelial cells. We show that B1a cells producing lipid‐reactive aPL of the IgG isotype circulate in the blood of COVID‐19 patients. In vivo, COVID‐19 aPL accelerate thrombus formation in an experimental mouse model dependent on the recently delineated signaling pathway involving EPCR‐LBPA. COVID‐19 patients rapidly expand B1a cells secreting pathogenic lipid‐binding aPL with broad thrombotic and inflammatory effects. The association with markers of inflammation and coagulation, clinical severity, and mortality suggests a causal role of aPL in COVID‐19–associated coagulopathy.
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DOI：
10.1126/science.abc0956
发表时间：
2021-03-12
期刊：
Science (New York, N.Y.)
影响因子：
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