Activation of coagulation and proinflammatory pathways in thrombosis with thrombocytopenia syndrome and following COVID-19 vaccination.
Activation of coagulation and proinflammatory pathways in thrombosis with thrombocytopenia syndrome and following COVID-19 vaccination.
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DOI：
10.1038/s41467-023-42559-x
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发表时间：
2023-10-23
影响因子：
16.6
通讯作者：
Barouch, Dan H.
中科院分区：
文献类型：
--
作者：
Aid, Malika;Stephenson, Kathryn E.;Collier, Ai-ris Y.;Nkolola, Joseph P.;Michael, James V.;Mckenzie, Steven E.;Barouch, Dan H.
血栓形成伴血小板减少综合征（TTS）是接种基于腺病毒载体的COVID-19疫苗（如Ad26.COV2）后发生的罕见但可能严重的不良事件。S（杨森）和ChAdOx1（阿斯利康）。然而，在接受Ad26.COV2第二次免疫的150多万人中，未报告发生TTS病例。S在美国。在这里，我们利用转录组学和蛋白质组学分析来比较接受两种剂量Ad26.COV2的个体。与接种了BNT162b2或mRNA-1273疫苗的人发生了S。初始Ad26.COV2。S疫苗可诱导血小板、凝血和先天免疫途径的短暂激活，并在第7天消退；相比之下，TTS患者在初始Ad26.COV2后15-19天表现出这些途径的强劲上调。疫苗接种。同时，第二次免疫或减少Ad26.COV2的初始剂量。S诱导的这些通路的激活比完全初始剂量低。我们的数据表明凝血和促炎途径在TTS发病机制中的作用，这可能有助于优化疫苗接种方案以降低TTS风险。基于腺病毒的SARS-CoV-2疫苗接种很少有机会引起血栓伴血小板减少症（TTS）。在这里，作者比较了接种TTS或未接种TTS疫苗的参与者的蛋白质组学和转录组学数据，以发现TTS患者或初次接种或加强接种后凝血和先天免疫途径的不同激活。
Thrombosis with thrombocytopenia syndrome (TTS) is a rare but potentially severe adverse event following immunization with adenovirus vector-based COVID-19 vaccines such as Ad26.COV2.S (Janssen) and ChAdOx1 (AstraZeneca). However, no case of TTS has been reported in over 1.5 million individuals who received a second immunization with Ad26.COV2.S in the United States. Here we utilize transcriptomic and proteomic profiling to compare individuals who receive two doses of Ad26.COV2.S with those vaccinated with BNT162b2 or mRNA-1273. Initial Ad26.COV2.S vaccination induces transient activation of platelet and coagulation and innate immune pathways that resolve by day 7; by contrast, patients with TTS show robust upregulation of these pathways on days 15–19 following initial Ad26.COV2.S vaccination. Meanwhile, a second immunization or a reduced initial dose of Ad26.COV2.S induces lower activation of these pathways than does the full initial dose. Our data suggest a role of coagulation and proinflammatory pathways in TTS pathogenesis, which may help optimize vaccination regimens to reduce TTS risk. Adenovirus-based vaccination for SARS-CoV-2 has a rare chance to cause thrombosis with thrombocytopenia (TTS). Here the authors compare proteomic and transcriptomic data from vaccinated participants with or without TTS to find distinct activations of coagulation and innate immune pathways in patient with TTS, or following initial or boosting vaccination.
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