Moser Tobias, O'Sullivan Ciara, Otto Ferdinand, Hitzl Wolfgang, Pilz Georg, Schwenker Kerstin, Mrazek Cornelia, Haschke-Becher Elisabeth, Trinka Eugen, Wipfler Peter, Harrer Andrea
Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University and Center for Cognitive Neuroscience, European Reference Network EpiCARE, Ignaz-Harrer-Straße 79, 5020 Salzburg, Austria.
Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University and Center for Cognitive Neuroscience, European Reference Network EpiCARE, Salzburg, Austria.
Ther Adv Neurol Disord. 2022 Apr 22;15:17562864221092092. doi: 10.1177/17562864221092092. eCollection 2022.
Anti-CD20 therapies induce pronounced B-cell depletion and blunt humoral responses to vaccines. Recovery kinetics of anti-CD20 therapy-mediated cellular and humoral effects in people with multiple sclerosis (pwMS) are poorly defined.
To investigate the duration of the anti-CD20 treatment-induced effects on humoral responses to COVID-19 vaccines.
This retrospective observational study included pwMS who had discontinued anti-CD20 therapy for ⩾12 months and remained without immunomodulation. We retrieved demographics and laboratory parameters including B-cell counts and immunoglobulin (IgG, IgM, IgA) levels prior to anti-CD20 commencement (baseline) and longitudinally after anti-CD20 treatment discontinuation from electronic medical records. Humoral responses to SARS-CoV-2 vaccines were compared with a population of 11 pwMS with ongoing anti-CD20 medication (control cohort).
A total of 24 pwMS had discontinued anti-CD20 therapy for a median of 34 months (range: 16-38 months). Antibody responses to COVID-19 vaccines were available in 17 (71%). Most individuals ( = 15, 88%) elicited a measurable antibody response [mean: 774 BAU/ml (±SD 1283 BAU/ml)] to SARS-CoV-2 immunization on average 22 months (range: 10-30 months) from the last anti-CD20 infusion, which was higher compared with the population with ongoing anti-CD20 therapy ( = 11, mean: 12.36 ± SD 11.94 BAU/ml; < 0.00001). Significantly increased antibody levels compared with the control cohort were found among pwMS who were vaccinated >18 months after treatment discontinuation (19-24 months: = 2, = 0.013; 25-36 months: = 9; < 0.001). The interindividual kinetics for B-cell reconstitution were heterogeneous and mean B-cell counts approached normal ranges 18 months after treatment discontinuation. There was no correlation of B-cell repopulation and vaccine responses. Mean total IgG, IgM, and IgA levels remained within the reference range.
Anti-CD20-induced inhibition of humoral responses to COVID-19 vaccines is transient and antibody production was more pronounced >18 months after anti-CD20 treatment discontinuation. The immunological effect on B-cell counts appears to wane by the same time.
抗CD20疗法可导致明显的B细胞耗竭，并削弱对疫苗的体液免疫反应。抗CD20疗法介导的细胞和体液效应在多发性硬化症患者（pwMS）中的恢复动力学尚不明确。
研究抗CD20治疗对COVID-19疫苗体液免疫反应的影响持续时间。
这项回顾性观察性研究纳入了已停用抗CD20疗法至少12个月且未进行免疫调节的pwMS。我们从电子病历中获取了人口统计学和实验室参数，包括抗CD20治疗开始前（基线）以及抗CD20治疗停药后的纵向B细胞计数和免疫球蛋白（IgG、IgM、IgA）水平。将对SARS-CoV-2疫苗的体液免疫反应与11名正在接受抗CD20治疗的pwMS人群（对照队列）进行比较。
共有24名pwMS停用抗CD20疗法，中位时间为34个月（范围：16 - 38个月）。17名（71%）患者有COVID-19疫苗的抗体反应数据。大多数个体（n = 15，88%）在最后一次抗CD20输注后平均22个月（范围：10 - 30个月）对SARS-CoV-2免疫接种产生了可测量的抗体反应[平均值：774 BAU/ml（±标准差1283 BAU/ml）]，这一数值高于正在接受抗CD20治疗的人群（n = 11，平均值：12.36 ±标准差11.94 BAU/ml；P < 0.00001）。在治疗停药>18个月后接种疫苗的pwMS中发现抗体水平与对照队列相比显著升高（19 - 24个月：n = 2，P = 0.013；25 - 36个月：n = 9；P < 0.001）。B细胞重建的个体间动力学存在异质性，治疗停药后18个月平均B细胞计数接近正常范围。B细胞再增殖与疫苗反应之间没有相关性。总IgG、IgM和IgA水平的平均值仍在参考范围内。
抗CD20诱导的对COVID-19疫苗体液免疫反应的抑制是短暂的，抗CD20治疗停药>18个月后抗体产生更为明显。对B细胞计数的免疫效应似乎在同一时间减弱。
