Type I interferon, anti-interferon antibodies, and COVID-19.
Type I interferon, anti-interferon antibodies, and COVID-19.
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DOI：
10.1016/s2665-9913(21)00034-5
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发表时间：
2021-04
期刊：
影响因子：
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通讯作者：
Walter JE
中科院分区：
文献类型：
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作者：
Calabrese LH;Winthrop K;Strand V;Yazdany J;Walter JE
在过去的一年里，我们对 COVID-19 免疫生物学的了解取得了巨大进展，为了解干扰素在针对严重急性呼吸综合征冠状病毒 2 的免疫反应中的中心地位提供了重要见解。多项研究证明了干扰素的参与。例如，Zhang 及其同事1对一大批重症 COVID-19 患者进行了筛查，检查与 Toll 样受体信号分子和在严重流感和其他病毒感染病例中发现的 I 型干扰素通路相关的 13 个基因中是否存在预测的功能丧失变异。在 659 名重症 COVID-19 患者中，23 名 (3·5%) 的 8 个基因存在已知或新突变，证明了这些途径在病毒防御中的重要性。在第二项研究中，Bastard 及其同事2 报告了一项显着的发现，即 987 名危及生命的 COVID-19 患者中，有 135 名（13·7%）携带针对 I 型干扰素的自身抗体（主要针对干扰素 [IFN]-α2 和 IFN-ω），其中大多数在体外表现出中和能力。此类抗体仅在 1227 名未暴露的健康个体中的 4 名 (0·3%) 中检测到。这些论文进一步证实了干扰素在 COVID-19 中的重要性，这对风湿病学领域有直接和间接的影响。特别重要的是，这些数据可能如何影响一类新型生物制剂的开发计划，该生物制剂旨在治疗系统性红斑狼疮 (SLE) 及相关疾病患者的 I 型干扰素通路。天然存在的针对细胞因子的自身抗体的记录并不引人注目，因为在健康献血者的研究中报告了低浓度的此类抗体，这表明大多数献血者都含有微量抗体。 3 在对 8972 名献血者中针对包括 I 型干扰素在内的五种细胞因子的抗体流行率进行的最大规模的研究中，在不到 1% 的参与者中发现了高浓度的 I 型干扰素抗体，与年龄、性别或吸烟等变量没有流行病学关联，3 与 COVID-19 研究中对照人群的结果相似（I 型干扰素抗体< 1%）。 2 在静脉注射免疫球蛋白制剂和接受 I 型干扰素感染治疗的患者中也发现了这些自身抗体
In the past year, considerable gains in our understanding of the immunobiology of COVID-19 have provided key insights into the centrality of interferons in the immune response against severe acute respiratory syndrome corona virus 2. Several studies attest to the involvement of inter ferons. For instance, Zhang and colleagues1 screened a large cohort of patients with severe COVID-19 for the presence of predicted loss-of-function variants in 13 genes associated with Toll-like receptor signaling molecules and the type I interferon pathway identified in cases of severe influenza and other viral infections. Of 659 patients with severe COVID-19, 23 (3· 5%) harbored known or new mutations in eight of the genes, attesting to the importance of these pathways in viral defense. In a second study, Bastard and colleagues2 reported a remarkable finding that 135 (13· 7%) of 987 patients with life-threatening COVID-19 harboured autoantibodies against type I interferons (mostly against interferon [IFN]-α2 and IFN-ω) with most showing neutralising capacity in vitro. Such antibodies were only detected in 4 (0· 3%) of 1227 unexposed, healthy individuals. These papers add to a growing body of literature affirming the importance of interferons in COVID-19, which has direct and indirect implications for the field of rheumatology. Of particular and immediate importance is how these data might affect the development programme of a new class of biological agents designed to therapeutically target the type I interferon pathway in patients with systemic lupus erythematosus (SLE) and allied conditions.The documentation of naturally occurring autoantibodies against a cytokine is not remarkable, as low concentrations of such antibodies have been reported in studies of healthy blood donors, which showed most of the donors to have trace amounts. 3 In the largest study exam in ing the prevalence of antibodies against five cytokines including type I interferons in 8972 blood donors, high con centra tions of antibodies to type I interferons were found in less than 1% of participants, with no epidemi ological associations with variables such as age, sex, or smoking, 3 similar to findings in control populations (type I interferon anti bodies in< 1%) in the COVID-19 study. 2 These autoantibodies have also been found in intravenous immunoglobulin preparations and in patients undergoing therapy with type I interferon for infections