抗 CD20 治疗的多发性硬化症患者在接种 SARS-CoV-2 mRNA 疫苗后，T 细胞激活标志物 CD38 和 HLA-DR 提示未发生血清转化。
T cell activation markers CD38 and HLA-DR indicative of non-seroconversion in anti-CD20-treated patients with multiple sclerosis following SARS-CoV-2 mRNA vaccination.
机构信息
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
出版信息
J Neurol Neurosurg Psychiatry. 2024 Aug 16;95(9):855-864. doi: 10.1136/jnnp-2023-332224.
BACKGROUND
Messenger RNA (mRNA) vaccines provide robust protection against SARS-CoV-2 in healthy individuals. However, immunity after vaccination of patients with multiple sclerosis (MS) treated with ocrelizumab (OCR), a B cell-depleting anti-CD20 monoclonal antibody, is not yet fully understood.
METHODS
In this study, deep immune profiling techniques were employed to investigate the immune response induced by SARS-CoV-2 mRNA vaccines in untreated patients with MS (n=21), OCR-treated patients with MS (n=57) and healthy individuals (n=30).
RESULTS
Among OCR-treated patients with MS, 63% did not produce detectable levels of antibodies (non-seroconverted), and those who did have lower spike receptor-binding domain-specific IgG responses compared with healthy individuals and untreated patients with MS. Before vaccination, no discernible immunological differences were observed between non-seroconverted and seroconverted OCR-treated patients with MS. However, non-seroconverted patients received overall more OCR infusions, had shorter intervals since their last OCR infusion and displayed higher OCR serum concentrations at the time of their initial vaccination. Following two vaccinations, non-seroconverted patients displayed smaller B cell compartments but instead exhibited more robust activation of general CD4 and CD8 T cell compartments, as indicated by upregulation of CD38 and HLA-DR surface expression, when compared with seroconverted patients.
CONCLUSION
These findings highlight the importance of optimising treatment regimens when scheduling SARS-CoV-2 vaccination for OCR-treated patients with MS to maximise their humoral and cellular immune responses. This study provides valuable insights for optimising vaccination strategies in OCR-treated patients with MS, including the identification of CD38 and HLA-DR as potential markers to explore vaccine efficacy in non-seroconverting OCR-treated patients with MS.
背景
信使 RNA（mRNA）疫苗在健康个体中提供了针对 SARS-CoV-2 的强大保护。然而，奥瑞珠单抗（OCR）治疗的多发性硬化症（MS）患者接种疫苗后的免疫反应尚不完全清楚，OCR 是一种 B 细胞耗竭性抗 CD20 单克隆抗体。
方法
在这项研究中，采用深度免疫分析技术研究了未经治疗的 MS 患者（n=21）、OCR 治疗的 MS 患者（n=57）和健康个体（n=30）接种 SARS-CoV-2 mRNA 疫苗后诱导的免疫反应。
结果
在 OCR 治疗的 MS 患者中，有 63%的患者未检测到抗体（未发生血清转化），且与健康个体和未经治疗的 MS 患者相比，这些患者的刺突受体结合域特异性 IgG 反应较低。在接种疫苗之前，未发生血清转化的 OCR 治疗的 MS 患者和发生血清转化的患者之间未观察到明显的免疫差异。然而，未发生血清转化的患者接受了更多的 OCR 输注，最后一次 OCR 输注的间隔时间较短，并且在初始接种时 OCR 血清浓度更高。接种两剂疫苗后，与发生血清转化的患者相比，未发生血清转化的患者表现出较小的 B 细胞群，但表现出更强烈的一般 CD4 和 CD8 T 细胞群的激活，这表现为 CD38 和 HLA-DR 表面表达的上调。
结论
这些发现强调了在为 OCR 治疗的 MS 患者安排 SARS-CoV-2 疫苗接种时优化治疗方案的重要性，以最大程度地提高其体液和细胞免疫反应。这项研究为优化 OCR 治疗的 MS 患者的疫苗接种策略提供了有价值的见解，包括将 CD38 和 HLA-DR 鉴定为探索非血清转化的 OCR 治疗的 MS 患者疫苗疗效的潜在标志物。
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