Akbayir Ece, Kizilay Tugce, Erol Ruziye, Ozkan-Yasargun Duygu, Tuzun Erdem, Yilmaz Vuslat, Turkoglu Recai
Department of Neuroscience, Aziz Sancar Institute for Experimental Medical Research, Istanbul University, Istanbul, Turkiye;
Department of Language and Speech Therapy, Faculty of Health Sciences, Istanbul Atlas University, Istanbul, Turkiye.
In Vivo. 2025 Mar-Apr;39(2):1162-1172. doi: 10.21873/invivo.13920.
BACKGROUND/AIM: Ocrelizumab, a CD20-targeting monoclonal antibody, is used for treatment of multiple sclerosis. The aim of this study was to explore the utility of peripheral blood cell subsets in prediction of treatment response to ocrelizumab in relapsing remitting multiple sclerosis (RRMS).
Thirty-one patients with RRMS resistant to first-line immunomodulating agents were enrolled and followed-up for 12 months under ocrelizumab treatment. Disease activity was monitored by 6-monthly assessments of Expanded Disability Status Scale and cranial-spinal magnetic resonance imaging. No evidence of disease activity (NEDA-3) status was determined, and peripheral blood mononuclear cells were immunophenotyped by flow cytometry.
Peripheral blood populations of CD19 B-cells, plasma cells and CD3 CD20 T-cells decreased under ocrelizumab therapy, whereas populations of switched memory B-cells, CD4 T-cells, naïve T-cells and regulatory B-1a and CD49d T-cells were increased. NEDA-3 status was achieved by 19 patients, who exhibited elevated baseline populations of regulatory CD49d T- and B-1a-cells, reduced post-treatment (month 6 or 12) populations of switched memory B-cells, and increased post-treatment populations of naïve T-cells. Month 12 Expanded Disability Status Scale scores correlated positively with plasmablast and naïve T-cell populations.
Response to ocrelizumab is linked to baseline regulatory and post-treatment effector B- and T-cell subset populations. Memory B-cells appear to be a marker of treatment efficacy for ocrelizumab.
背景/目的:奥瑞珠单抗是一种靶向CD20的单克隆抗体,用于治疗多发性硬化症。本研究的目的是探讨外周血细胞亚群在预测复发缓解型多发性硬化症(RRMS)患者对奥瑞珠单抗治疗反应中的作用。
纳入31例对一线免疫调节药物耐药的RRMS患者,接受奥瑞珠单抗治疗并随访12个月。通过每6个月评估扩展残疾状态量表和头颅脊髓磁共振成像监测疾病活动情况。确定无疾病活动证据(NEDA-3)状态,并通过流式细胞术对外周血单个核细胞进行免疫表型分析。
在奥瑞珠单抗治疗下,外周血中CD19 B细胞、浆细胞和CD3 CD20 T细胞数量减少,而转换记忆B细胞、CD4 T细胞、初始T细胞以及调节性B-1a细胞和CD49d T细胞数量增加。19例患者达到NEDA-3状态,这些患者基线时调节性CD49d T细胞和B-1a细胞数量升高,治疗后(第6或12个月)转换记忆B细胞数量减少,治疗后初始T细胞数量增加。第12个月的扩展残疾状态量表评分与浆母细胞和初始T细胞数量呈正相关。
对奥瑞珠单抗的反应与基线调节性以及治疗后效应性B细胞和T细胞亚群数量有关。记忆B细胞似乎是奥瑞珠单抗治疗疗效的一个标志物。