Paradoxical sex-specific patterns of autoantibody response to SARS-CoV-2 infection.
Paradoxical sex-specific patterns of autoantibody response to SARS-CoV-2 infection.
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DOI：
10.1186/s12967-021-03184-8
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发表时间：
2021-12-30
影响因子：
7.4
通讯作者：
Fert-Bober J
中科院分区：
文献类型：
--
作者：
Liu Y;Ebinger JE;Mostafa R;Budde P;Gajewski J;Walker B;Joung S;Wu M;Bräutigam M;Hesping F;Rupieper E;Schubert AS;Zucht HD;Braun J;Melmed GY;Sobhani K;Arditi M;Van Eyk JE;Cheng S;Fert-Bober J
对SARS-CoV-2感染易感性和反应的明显性别差异仍知之甚少。新出现的证据强调了自身免疫激活在调节SARS-CoV-2暴露后的急性反应和恢复轨迹方面的潜在重要性。鉴于在COVID-19严重疾病的情况下，免疫炎症活动可能存在性别偏见，因此该研究的目的是在没有极端临床疾病的情况下检查性别特异性自身免疫对SARS-CoV-2的反应。在这项研究中，我们在177名参与者（65%女性，35%男性，平均年龄35岁）中评估了自身抗体（AAB）对91种先前与一系列经典自身免疫性疾病相关的自身抗原的反应性，基于对SARS-CoV-2核衣壳蛋白抗体的存在，确认了先前感染SARS-CoV-2的证据。将数据与53个大流行前健康对照（49%为女性，51%为男性）进行比较。通过电子问卷调查收集每位参与者的社会人口学数据、血清学分析、SARS-CoV-2感染状况和COVID-19相关症状。症状负担评分是根据抽血前6个月内报告的症状总数（N = 21）构建的，其中症状数量越多，评分越高，负担越重。在多变量分析中，我们观察到与既往COVID-19疾病相关的存在或不存在（以及症状的时间和聚类）相关的自身反应性的性别特异性模式。在无症状感染后，AAB的总体反应在女性中更为突出，而在至少轻度症状感染后，AAB反应的广度和程度在男性中更为突出。值得注意的是，观察到的反应性包括与SARS-CoV-2具有分子同源性的不同抗原。我们的研究结果表明，即使在没有严重临床疾病的情况下，先前的SARS-CoV-2感染也可能导致广泛的AAB反应，表现出性别特异性的患病率和抗原选择性模式。进一步了解暴露于SARS-CoV-2的男性和女性中触发的AAB激活的性质，对于制定针对COVID-19免疫介导的后遗症的有效干预措施至关重要。在线版本包含补充材料，可在10.1186/s12967-021-03184-8获得。
Pronounced sex differences in the susceptibility and response to SARS-CoV-2 infection remain poorly understood. Emerging evidence has highlighted the potential importance of autoimmune activation in modulating the acute response and recovery trajectories following SARS-CoV-2 exposure. Given that immune-inflammatory activity can be sex-biased in the setting of severe COVID-19 illness, the aim of the study was to examine sex-specific autoimmune reactivity to SARS-CoV-2 in the absence of extreme clinical disease. In this study, we assessed autoantibody (AAB) reactivity to 91 autoantigens previously linked to a range of classic autoimmune diseases in a cohort of 177 participants (65% women, 35% men, mean age of 35) with confirmed evidence of prior SARS-CoV-2 infection based on presence of antibody to the nucleocapsid protein of SARS-CoV-2. Data were compared to 53 pre-pandemic healthy controls (49% women, 51% men). For each participant, socio-demographic data, serological analyses, SARS-CoV-2 infection status and COVID-19 related symptoms were collected by an electronic survey of questions. The symptoms burden score was constructed based on the total number of reported symptoms (N = 21) experienced within 6 months prior to the blood draw, wherein a greater number of symptoms corresponded to a higher score and assigned as more severe burden. In multivariable analyses, we observed sex-specific patterns of autoreactivity associated with the presence or absence (as well as timing and clustering of symptoms) associated with prior COVID-19 illness. Whereas the overall AAB response was more prominent in women following asymptomatic infection, the breadth and extent of AAB reactivity was more prominent in men following at least mildly symptomatic infection. Notably, the observed reactivity included distinct antigens with molecular homology with SARS-CoV-2. Our results reveal that prior SARS-CoV-2 infection, even in the absence of severe clinical disease, can lead to a broad AAB response that exhibits sex-specific patterns of prevalence and antigen selectivity. Further understanding of the nature of triggered AAB activation among men and women exposed to SARS-CoV-2 will be essential for developing effective interventions against immune-mediated sequelae of COVID-19. The online version contains supplementary material available at 10.1186/s12967-021-03184-8.
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影响因子：
5.1
作者：
Billi AC;Kahlenberg JM;Gudjonsson JE
通讯作者：
Gudjonsson JE
影响因子：
2.8
作者：
Fukushima, Hidetaka;Matsuo, Hideaki;Yoshimura, Tetsuro
通讯作者：
Yoshimura, Tetsuro
影响因子：
2.6
作者：
Budde, P.;Zucht, H-D;Schneider, M.
通讯作者：
Schneider, M.
影响因子：
14.9
作者：
Choi J;Hwang SY;Ahn K
通讯作者：
Ahn K
影响因子：
4.6
作者：
Daamen AR;Bachali P;Owen KA;Kingsmore KM;Hubbard EL;Labonte AC;Robl R;Shrotri S;Grammer AC;Lipsky PE
通讯作者：
Lipsky PE