Immune complexes, innate immunity, and NETosis in ChAdOx1 vaccine-induced thrombocytopenia.
Immune complexes, innate immunity, and NETosis in ChAdOx1 vaccine-induced thrombocytopenia.
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DOI：
10.1093/eurheartj/ehab506
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发表时间：
2021-10-14
影响因子：
39.3
通讯作者：
Halvorsen B
中科院分区：
文献类型：
--
作者：
Holm S;Kared H;Michelsen AE;Kong XY;Dahl TB;Schultz NH;Nyman TA;Fladeby C;Seljeflot I;Ueland T;Stensland M;Mjaaland S;Goll GL;Nissen-Meyer LS;Aukrust P;Skagen K;Gregersen I;Skjelland M;Holme PA;Munthe LA;Halvorsen B
我们最近报告了5例疫苗诱导的免疫性血栓性血小板减少症(VITT)病例，在接种首剂ChAdOx1nCoV-19腺病毒载体疫苗(新冠肺炎)后7-10 天。我们的目的是研究这些患者的致病免疫反应。我们用免疫分析法检测循环炎症标志物，用流式细胞仪分析免疫细胞表型，并用抗血小板因子(PF)4抗体在血浆样本中进行免疫沉淀，然后对所有5名患者进行质谱分析。从1例患者的鼻窦矢状面上取血栓，用免疫组织化学和流式细胞术进行分析。沉淀免疫复合体揭示了多种天然免疫途径触发的血小板和白细胞的激活。血浆中含有升高的先天免疫反应细胞因子和全身炎症、中性粒细胞广泛脱颗粒以及组织和内皮损伤的标志物。血液分析显示中性粒细胞激活，循环H3Cit、双链DNA和髓过氧化物酶-DNA复合体水平增加。血栓有广泛的中性粒细胞浸润，形成中性粒细胞细胞外陷阱(Net)，并有IgG沉着。结果表明，抗PF4/聚阴离子免疫球蛋白介导的血栓形成伴随着大量的天然免疫激活，尤其是中性粒细胞的暴发性激活，包括网织红细胞增多。这些结果为这种罕见的腺病毒载体诱导的VITT的免疫反应提供了新的数据。
We recently reported five cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) 7–10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against corona virus disease 2019 (COVID-19). We aimed to investigate the pathogenic immunological responses operating in these patients. We assessed circulating inflammatory markers by immune assays and immune cell phenotyping by flow cytometry analyses and performed immunoprecipitation with anti-platelet factor (PF)4 antibody in plasma samples followed by mass spectrometry from all five patients. A thrombus was retrieved from the sinus sagittal superior of one patient and analysed by immunohistochemistry and flow cytometry. Precipitated immune complexes revealed multiple innate immune pathway triggers for platelet and leucocyte activation. Plasma contained increased levels of innate immune response cytokines and markers of systemic inflammation, extensive degranulation of neutrophils, and tissue and endothelial damage. Blood analyses showed activation of neutrophils and increased levels of circulating H3Cit, dsDNA, and myeloperoxidase–DNA complex. The thrombus had extensive infiltration of neutrophils, formation of neutrophil extracellular traps (NETs), and IgG deposits. The results show that anti-PF4/polyanion IgG-mediated thrombus formation in VITT patients is accompanied by a massive innate immune activation and particularly the fulminant activation of neutrophils including NETosis. These results provide novel data on the immune response in this rare adenoviral vector-induced VITT.
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影响因子：
5.1
作者：
Appledorn, D. M.;Kiang, A.;Amalfitano, A.
通讯作者：
Amalfitano, A.
参与肝素诱导的血小板减少症的免疫复合物的原子描述。
影响因子：
16.6
作者：
Cai Z;Yarovoi SV;Zhu Z;Rauova L;Hayes V;Lebedeva T;Liu Q;Poncz M;Arepally G;Cines DB;Greene MI
通讯作者：
Greene MI
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
影响因子：
20.3
作者：
Chen, Kan;Nishi, Hiroshi;Mayadas, Tanya N.
通讯作者：
Mayadas, Tanya N.
影响因子：
8
作者：
Gollomp, Kandace;Kim, Minna;Poncz, Mortimer
通讯作者：
Poncz, Mortimer