Anti-PF4 antibodies associated with disease severity in COVID-19.
Anti-PF4 antibodies associated with disease severity in COVID-19.
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抗PF 4抗体与COVID-19疾病严重程度相关。
DOI：
10.1073/pnas.2213361119
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发表时间：
2022-11-22
影响因子：
11.1
通讯作者：
Lusso, Paolo
中科院分区：
文献类型：
--
作者：
Liu, Qingbo;Miao, Huiyi;Li, Shuai;Zhang, Peng;Gerber, Gloria F.;Follmann, Dean;Ji, Hongkai;Zeger, Scott L.;Chertow, Daniel S.;Quinn, Thomas C.;Robinson, Matthew L.;Kickler, Thomas S.;Rothman, Richard E.;Fenstermacher, Katherine Z. J.;Braunstein, Evan M.;Cox, Andrea L.;Farci, Patrizia;Fauci, Anthony S.;Lusso, Paolo
触发新冠肺炎最严重并发症的致病机制在很大程度上仍不清楚。在肺部和其他器官中发现了广泛的微观血栓形成，表明凝血异常参与了发病过程。这项研究表明，几乎所有严重新冠肺炎的患者都会产生针对内源性蛋白--血小板第4因子(PF4)的异常抗体，这是以血栓形成和血小板减少为特征的两种危及生命的疾病的特征：肝素诱导的血小板减少和疫苗诱导的血栓形成伴血小板减少。抗PF4抗体是两种危及生命的疾病的标志：肝素诱导的血小板减少症和疫苗诱导的血栓形成伴血小板减少症。最严重的疾病和最明显的血小板减少的患者的抗体水平更高。提示抗PF4抗体可能在新冠肺炎严重的多脏器疾病表现中起一定作用。重症新冠肺炎的特征是血栓前状态与血小板减少相关，尸检时几乎总是在肺和其他器官出现微血管血栓。我们用临床验证的免疫分析方法评估了100例中重度新冠肺炎住院患者(世界卫生组织评分4~10)、25例急诊新冠肺炎急性患者和65例恢复期患者的血小板第4因子-多阴离子复合体抗体的存在。新冠肺炎患者中95例(95.0%)检出抗PF4抗体，平均光密度值为0.871±0.405 SD(范围0.177~2.706)。相比之下，因与新冠肺炎无关的严重急性呼吸道疾病住院的患者的抗体水平明显较低。在高比例的新冠肺炎患者中，所有三种免疫球蛋白(Ig)亚型(Ig、Ig M和Ig A)的水平同时升高。男性患者的抗体水平高于女性患者，非裔美国人和西班牙裔患者的抗体水平高于白人患者。抗PF4抗体水平与最大疾病严重程度评分和住院期间循环血小板计数显著减少相关。在新冠肺炎恢复期的患者中，抗体水平恢复到接近正常值。新冠肺炎患者血清诱导的血小板活化水平高于健康献血者，但与抗PF4抗体水平无相关性。这些结果表明，绝大多数重症新冠肺炎患者都产生了抗PF4抗体，这可能在新冠肺炎的临床并发症中发挥了作用。
The pathogenic mechanisms that trigger the most severe complications of COVID-19 are still largely unknown. Widespread formation of microscopic thrombi has been detected in the lungs and other organs, suggesting that coagulation abnormalities are involved in the pathogenic process. This study shows that virtually all patients with severe COVID-19 develop anomalous antibodies that target an endogenous protein, platelet factor 4 (PF4), and that are the hallmark of two life-threatening disorders characterized by thrombosis and thrombocytopenia: heparin-induced thrombocytopenia and vaccine-induced thrombosis with thrombocytopenia. Anti-PF4 antibodies are the hallmark of two life-threatening disorders: heparin-induced thrombocytopenia and vaccine-induced thrombosis with thrombocytopenia. Higher antibody levels were found in patients with the most severe disease and the most conspicuous platelet reductions. These findings suggest that anti-PF4 antibodies may play a role in the severe multiorgan disease manifestations of COVID-19. Severe COVID-19 is characterized by a prothrombotic state associated with thrombocytopenia, with microvascular thrombosis being almost invariably present in the lung and other organs at postmortem examination. We evaluated the presence of antibodies to platelet factor 4 (PF4)–polyanion complexes using a clinically validated immunoassay in 100 hospitalized patients with COVID-19 with moderate or severe disease (World Health Organization score, 4 to 10), 25 patients with acute COVID-19 visiting the emergency department, and 65 convalescent individuals. Anti-PF4 antibodies were detected in 95 of 100 hospitalized patients with COVID-19 (95.0%) irrespective of prior heparin treatment, with a mean optical density value of 0.871 ± 0.405 SD (range, 0.177 to 2.706). In contrast, patients hospitalized for severe acute respiratory disease unrelated to COVID-19 had markedly lower levels of the antibodies. In a high proportion of patients with COVID-19, levels of all three immunoglobulin (Ig) isotypes tested (IgG, IgM, and IgA) were simultaneously elevated. Antibody levels were higher in male than in female patients and higher in African Americans and Hispanics than in White patients. Anti-PF4 antibody levels were correlated with the maximum disease severity score and with significant reductions in circulating platelet counts during hospitalization. In individuals convalescent from COVID-19, the antibody levels returned to near-normal values. Sera from patients with COVID-19 induced higher levels of platelet activation than did sera from healthy blood donors, but the results were not correlated with the levels of anti-PF4 antibodies. These results demonstrate that the vast majority of patients with severe COVID-19 develop anti-PF4 antibodies, which may play a role in the clinical complications of COVID-19.
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BNT162B2 mRNA COVID-19疫苗的安全性和功效。
DOI：
10.1056/nejmoa2034577
发表时间：
2020-12-31
期刊：
The New England journal of medicine
影响因子：
--
作者：
Polack FP;Thomas SJ;Kitchin N;Absalon J;Gurtman A;Lockhart S;Perez JL;Pérez Marc G;Moreira ED;Zerbini C;Bailey R;Swanson KA;Roychoudhury S;Koury K;Li P;Kalina WV;Cooper D;Frenck RW Jr;Hammitt LL;Türeci Ö;Nell H;Schaefer A;Ünal S;Tresnan DB;Mather S;Dormitzer PR;Şahin U;Jansen KU;Gruber WC;C4591001 Clinical Trial Group
通讯作者：
C4591001 Clinical Trial Group
DOI：
10.1056/nejmoa2104840
发表时间：
2021-06-03
期刊：
The New England journal of medicine
影响因子：
--
作者：
Greinacher A;Thiele T;Warkentin TE;Weisser K;Kyrle PA;Eichinger S
通讯作者：
Eichinger S
DOI：
10.1073/pnas.1207314109
发表时间：
2012-06-12
影响因子：
11.1
作者：
Auerbach, David J.;Lin, Yin;Lusso, Paolo
通讯作者：
Lusso, Paolo
影响因子：
158.5
作者：
Ackermann, Maximilian;Verleden, Stijn E.;Jonigk, Danny
通讯作者：
Jonigk, Danny
影响因子：
64.5
作者：
Corti D;Purcell LA;Snell G;Veesler D
通讯作者：
Veesler D