Abstract:
Acute SARS-CoV-2 infection triggers the generation of diverse and functional autoantibodies (AABs), even after mild cases. Persistently elevated autoantibodies have been found in some individuals with long COVID (LC). Using a >21,000 human protein array, we identified diverse AAB targets in LC patients that correlated with their symptoms. Elevated AABs to proteins in the nervous system were found in LC patients with neurocognitive and neurological symptoms. Purified Immunoglobulin G (IgG) samples from these individuals reacted with human pons tissue and were cross-reactive with mouse sciatic nerves, spinal cord, and meninges. Antibody reactivity to sciatic nerves and meninges correlated with patient-reported headache and disorientation. Passive transfer of IgG from patients to mice led to increased sensitivity and pain, mirroring patient-reported symptoms. Similarly, mice injected with IgG showed loss of balance and coordination, reflecting donor-reported dizziness. Our findings suggest that targeting AABs could benefit some LC patients.
摘要:
急性SARS-CoV-2感染会引发多种功能性自身抗体(AAB)的产生,即使在轻度病例之后。在一些患有长期COVID(LC)的个体中发现了持续升高的自身抗体。使用>21,000的人类蛋白质阵列,我们在LC患者中确定了与其症状相关的不同AAB靶点.在具有神经认知和神经系统症状的LC患者中发现了神经系统中蛋白质的AAB升高。来自这些个体的纯化免疫球蛋白G(IgG)样品与人桥组织反应,并与小鼠坐骨神经交叉反应,脊髓,和脑膜。对坐骨神经和脑膜的抗体反应性与患者报告的头痛和定向障碍有关。IgG从患者被动转移到小鼠导致敏感性和疼痛增加,反映患者报告的症状。同样,注射IgG的小鼠表现出失去平衡和协调,反映捐赠者报告的头晕。我们的研究结果表明,靶向AAB可以使一些LC患者受益。