From the Department of Neurology (N.M.), the University of Texas Southwestern Medical Center, Dallas; Departments of Pediatrics and Neurology and Neurological Sciences (L.S.), Stanford University, CA; and Neurology Section (O.S.), VA North Texas Health Care System, Medical Service Dallas, VA Medical Center.
Neurol Neuroimmunol Neuroinflamm. 2020 Dec 24;8(2). doi: 10.1212/NXI.0000000000000935. Print 2021 Mar.
To discuss the pathogenic and diagnostic relevance of cellular and humoral immune responses against severe acute respiratory syndrome novel coronavirus (SARS-COV-2) and pertinent observations made in progressive multifocal leukoencephalopathy (PML).
Review of pertinent literature RESULTS: There is at least 1 precedent for an antibody response against a viral pathogen that fails to provide host protection in the absence of immune-competent CD4 T cells. PML is an infection of the CNS caused by JC virus (JCV), which commonly occurs during treatment with the therapeutic monoclonal antibody natalizumab. In this context, the humoral immune response fails to prevent JCV reactivation, and elevated anti-JCV serum indices are associated with a higher PML incidence. The more relevant immune-competent cells in host defense against JCV appear to be T cells. T cell-mediated responses are also detectable in convalescing patients with SARS-COV-2 irrespective of the humoral immune response.
Based on pathogenic lessons learned from PML under natalizumab therapy, we suggest the incorporation of functional assays that determine neutralizing properties of SARS-CoV-2-specific antibodies. In addition, we outline the potential role of T-cell detection assays in determining herd immunity in a given population or in studying therapeutic responses to vaccines.
讨论针对严重急性呼吸综合征新型冠状病毒（SARS-CoV-2）的细胞和体液免疫反应的发病机制和诊断相关性，并对进行性多灶性白质脑病（PML）中的相关观察结果进行讨论。
复习相关文献。
至少有一个先例表明，在缺乏免疫活性 CD4 T 细胞的情况下，针对病毒病原体的抗体反应未能提供宿主保护。PML 是一种由 JC 病毒（JCV）引起的中枢神经系统感染，通常发生在使用治疗性单克隆抗体那他珠单抗治疗期间。在这种情况下，体液免疫反应未能阻止 JCV 再激活，而升高的抗 JCV 血清指数与更高的 PML 发生率相关。在针对 JCV 的宿主防御中，更相关的免疫活性细胞似乎是 T 细胞。在 SARS-CoV-2 康复患者中，无论体液免疫反应如何，均可检测到 T 细胞介导的反应。
基于纳他珠单抗治疗下 PML 的发病机制经验，我们建议纳入功能性测定，以确定 SARS-CoV-2 特异性抗体的中和特性。此外，我们概述了 T 细胞检测测定在确定特定人群中的群体免疫或研究疫苗治疗反应方面的潜在作用。
