Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, Salzburg, Austria.
Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, Salzburg, Austria.
Mult Scler Relat Disord. 2021 Feb;48:102727. doi: 10.1016/j.msard.2020.102727. Epub 2020 Dec 29.
Recent data support a key role of B cells in the pathogenesis of multiple sclerosis. Due to the pronounced effect of cladribine on memory B cells, we initiated an immune phenotyping study, which included monitoring of memory B cells of patients newly assigned to this treatment option. A patient with ongoing disease activity in the first year of cladribine after a long-standing fingolimod treatment caught our attention.
To report about differences in the immune phenotype of the case compared to patients without disease activity and to discuss possible causes for the deviations as caveats regarding treatment sequelae.
Clinical data and immune phenotyping data collected at baseline (before treatment) and after three, six and ten/twelve months after cladribine initiation were compared between our case and six patients with a stable disease course (controls).
Both, the case and controls showed similar reductions of memory B cells in response to cladribine. The case however, showed an accelerated repopulation dynamic of naïve B cells with an almost 3-fold hyperrepopulation compared to baseline levels, and lower pre-treatment levels of CD4+ and CD8+ T cells and memory B cells compared to controls.
We propose a prolonged pre-treatment with fingolimod as possible cause for the lack of response to cladribine. Autoreactive cells sequestrated within lymph nodes may have evaded cladribine depletion on top of a delay of recirculating regulatory T cells. In addition, we want to raise awareness of the importance of monitoring T and B cells for bridging the current lack of evidence regarding sequencing therapies in the real life setting.
最近的数据支持 B 细胞在多发性硬化症发病机制中的关键作用。由于克拉屈滨对记忆 B 细胞有明显的作用，我们启动了一项免疫表型研究，其中包括监测新分配给该治疗方案的患者的记忆 B 细胞。一名患者在接受克拉屈滨治疗 1 年后，在长期接受芬戈莫德治疗后仍有疾病活动，引起了我们的注意。
报告该病例与无疾病活动患者的免疫表型差异，并讨论可能导致偏差的原因，以提示治疗后效应。
在开始克拉屈滨治疗前（基线）和治疗后 3、6 和 10/12 个月，我们比较了该病例与 6 名疾病稳定患者（对照组）的临床数据和免疫表型数据。
病例和对照组在克拉屈滨治疗后均显示记忆 B 细胞的相似减少。然而，病例显示出幼稚 B 细胞的快速再增殖动态，与基线水平相比几乎增加了 3 倍，并且与对照组相比，CD4+和 CD8+T 细胞以及记忆 B 细胞的预处理水平较低。
我们提出了延长前期使用芬戈莫德作为对克拉屈滨无反应的可能原因。淋巴结内的自身反应性细胞可能逃避了克拉屈滨的耗竭，同时也延迟了循环调节性 T 细胞的再循环。此外，我们希望提高对监测 T 和 B 细胞的重要性的认识，以弥补当前真实环境中缺乏关于序贯治疗证据的问题。
