Multiple Sclerosis Unit, Federico II University Hospital, Via Sergio Pansini 5, 80131, Naples, Italy.
Department of Public Health, Federico II University of Naples, Naples, Italy.
J Neurol. 2023 Jan;270(1):272-282. doi: 10.1007/s00415-022-11350-1. Epub 2022 Sep 1.
We aim to evaluate 3-year effects of ocrelizumab (humanized anti-CD20 monoclonal antibody for the treatment of multiple sclerosis (MS)) on lymphocytes, neutrophils and immunoglobulins: (1) when compared with pre-infusion assessment; (2) over the course of treatment; and (3) possible clinical correlates of the observed immunological modifications.
This real-world observational cohort study has been conducted on prospectively collected data from 78 MS patients (mean age 47.8 ± 10.5 years; females 48.7%) commencing on ocrelizumab from 2018, with mean follow-up of 36.5 ± 6.8 months. Clinical data and blood samples were collected every three months. Total lymphocyte count and subpopulations were assessed on peripheral blood using flow cytometry. Serum immunoglobulins were evaluated with nephelometry.
When compared with pre-infusion values, we observed reduction of total, CD19 and CD20 lymphocyte counts; however, after the first infusion, their levels remained substantially stable. Over time we observed a progressive reduction of CD8 lymphocytes, while no changes were observed for CD4, CD27, CD3CD27, and CD19CD27. After the first infusion, we observed reduction in IgG, which further decreased during the follow-up. Higher probability of EDSS progression was associated with reduced modulation of CD8 lymphocytes.
Ocrelizumab affects both humoral and cellular immune responses. Disability progression over the follow-up was associated with lower CD8 cytotoxic T-lymphocyte reduction. Changes in humoral response are immediate and sustained, while modulation of cellular immunity occurs progressively through regular re-treatment, and is related to clinical stability.
我们旨在评估奥瑞珠单抗（一种用于治疗多发性硬化症的人源化抗 CD20 单克隆抗体）对淋巴细胞、中性粒细胞和免疫球蛋白的 3 年影响：（1）与输注前评估相比；（2）在治疗过程中；以及（3）观察到的免疫学改变的可能临床相关性。
本真实世界观察性队列研究基于 2018 年开始接受奥瑞珠单抗治疗的 78 例 MS 患者（平均年龄 47.8±10.5 岁；女性 48.7%）前瞻性收集的数据进行，平均随访 36.5±6.8 个月。每三个月收集临床数据和血液样本。使用流式细胞术评估外周血中的总淋巴细胞计数和亚群。用散射比浊法评估血清免疫球蛋白。
与输注前值相比，我们观察到总淋巴细胞计数和 CD19、CD20 淋巴细胞计数减少；然而，在第一次输注后，它们的水平基本保持稳定。随着时间的推移，我们观察到 CD8 淋巴细胞逐渐减少，而 CD4、CD27、CD3CD27 和 CD19CD27 没有变化。在第一次输注后，我们观察到 IgG 减少，在随访过程中进一步降低。EDSS 进展的可能性更高与 CD8 淋巴细胞的减少调节相关。
奥瑞珠单抗影响体液和细胞免疫反应。随访期间的残疾进展与 CD8 细胞毒性 T 淋巴细胞减少有关。体液反应的变化是即时和持续的，而细胞免疫的调节则通过定期再治疗逐渐发生，并与临床稳定性有关。
