Lancet Rheumatology: 抑制IL-1和IL-6影响COVID-19患者抗SARS-CoV-2抗体的中和活性

2021-11-01 MedSci原创 MedSci原创

评估危及生命的COVID-19经IL-6抑制剂治疗后康复患者的抗SARS-CoV-2抗体的滴度及其中和能力随着时间的变化.

     淋巴器官中白介素 (IL)-6表达的时空动态影响抗病毒体液免疫和细胞适应性免疫之间的平衡。特别是细胞病变病毒通常诱导IL-6介导的幼稚CD4+ T细胞分化为滤泡辅助T细胞,促进产生有效的中和抗体反应。

      SARS-CoV-2是一种细胞病变病毒,可导致危及生命的肺炎,特征是适应不良的炎症反应,其中较高的血清IL-6水平与疾病严重程度相关。从严重的COVID-19中康复的患者会产生最有效的抗SARS-CoV-2中和抗体,现在正在研究这些人的恢复期血浆以获取单克隆抗体用于治疗。IL-6从大流行开始就被使用,目前已被批准用于治疗重症COVID-19的住院患者。鉴于IL-6在中和抗病毒体液免疫发展中的关键作用,研究者评估了危及生命的COVID-19IL-6抑制剂治疗后康复患者的抗SARS-CoV-2抗体的滴度及其中和能力随着时间的变化

      方法:研究了在圣拉斐尔医院(意大利米兰)收治的30名患有严重COVID-19肺炎并伴有过度炎症的患者。除标准治疗外,10名患者接受了当地标准治疗,另10名患者接受了抗IL-6受体单克隆抗体sarilumab5名患者)或托珠单抗(5名患者),最后10名接受IL-1受体拮抗剂阿那白滞素。所有30名患者之前都被纳入了其他关于托珠单抗、sarilumab和阿那白滞素的大型观察性研究。目前的研究得到了圣拉斐尔医院伦理委员会(编号34/int/2020)的批准,参与者签署了书面知情同意书。有关研究设计和治疗的详细信息在附录(第1-3页)中报告。对治疗前(第0天)、第30天和第60天获得的血清样本进行了抗受体结合域 (RBD) 抗体及其对SARS-CoV-2的体外中和活性的测试。

      结果:三组患者在基线人口统计学特征、实验室检查结果和呼吸参数方面相似。在第0天和第30天,所有组的抗RBD抗体水平相似,而在第60天,在接受IL-1 IL-6阻断剂治疗的患者中观察到较低但无统计学意义的中位抗体滴度(图 A)。第0 天的抗RBD抗体滴度与疾病严重程度相关的呼吸或实验室参数无关,包括淋巴细胞计数、PaO2/FiO2比率、乳酸脱氢酶、C反应蛋白、铁蛋白和IL-6水平。重要的是,与标准治疗相比,接受IL-1IL-6抑制剂治疗患者血清的中和活性显著降低,接受IL-1抑制剂治疗的患者的中和活性中值降低了33%(为50%,接受标准治疗的患者为83%),并且在第30天接受IL-6抑制剂治疗的患者中中和活性降低了39%(为44%)。同样,在第60天,接受IL-1抑制剂(32%)IL-6抑制剂(33%)治疗的患者中位中和活性与标准治疗(72%)相比有所降低。

     结论:IL-1IL-6抑制剂用于治疗重症COVID-19患者的疗法会影响抗SARS-CoV-2抗体的中和活性。如果这些发现在其他队列中得到证实,应仔细讨论用IL-1IL-6抑制剂治疗后的COVID-19康复患者的疫苗接种策略,以及最佳接种疫苗的时间。

 

出处:

E. Della-Torre, E. Criscuolo, M. Lanzillotta, M. Locatelli, N. Clementi, N. Mancini, L. Dagna, IL-1 and IL-6 inhibition affects the neutralising activity of anti-SARS-CoV-2 antibodies in patients with COVID-19, The Lancet Rheumatology. 

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    2022-04-24 hukaixun
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    2022-09-01 howi
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    2021-11-03 kzlchina
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    2021-11-03 小刀医生
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    2021-11-03 jjjiang0202

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