Wang Meng, Otto Carolin, Fernández Zapata Camila, Dehlinger Adeline, Gallaccio Gerardina, Diekmann Lisa-Marie, Niederschweiberer Moritz, Schindler Patrick, Körtvélyessy Peter, Kunkel Desiree, Paul Friedemann, Ruprecht Klemens, Böttcher Chotima
Experimental and Clinical Research Center, a Cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin, Berlin, Germany.
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental and Clinical Research Center, Lindenberger Weg 80, Berlin 13125, Germany.
iScience. 2025 Apr 8;28(5):112383. doi: 10.1016/j.isci.2025.112383. eCollection 2025 May 16.
Ocrelizumab, an anti-CD20 antibody, depletes CD20 B cells, which subsequently repopulate over months. Little is known about changes in other immune cell populations and molecular markers associated with B cell repopulation. Here, we performed a comprehensive characterization of immune cells from ocrelizumab-treated patients with multiple sclerosis (MS) using mass cytometry. About 50% of patients showed naive B cell repopulation after 6 months mainly with a transitional phenotype, whereas CD27 memory B cells only rarely repopulated. This repopulation was associated with a reduction of memory T cells and activated myeloid cells, as well as reduced expression of activation/migration markers in both cell types. A plasma proteomics analysis identified proteins including TNFRSF13C, associated with B cell depletion and repopulation. Plasma levels of neurofilament light-chain protein declined after ocrelizumab treatment was not linked with B cell repopulation. These findings identify potential soluble markers for monitoring of ocrelizumab treatment in MS.
奥瑞珠单抗是一种抗CD20抗体，可耗竭CD20 B细胞，这些细胞随后会在数月内重新填充。关于其他免疫细胞群的变化以及与B细胞重新填充相关的分子标志物，我们了解得很少。在这里，我们使用质谱流式细胞术对接受奥瑞珠单抗治疗的多发性硬化症（MS）患者的免疫细胞进行了全面表征。约50%的患者在6个月后出现初始B细胞重新填充，主要表现为过渡表型，而CD27记忆B细胞很少重新填充。这种重新填充与记忆T细胞和活化髓样细胞的减少以及两种细胞类型中活化/迁移标志物表达的降低有关。血浆蛋白质组学分析确定了包括TNFRSF13C在内的与B细胞耗竭和重新填充相关的蛋白质。奥瑞珠单抗治疗后神经丝轻链蛋白的血浆水平下降，这与B细胞重新填充无关。这些发现确定了用于监测MS患者奥瑞珠单抗治疗的潜在可溶性标志物。
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