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长期使用利妥昔单抗可增加多发性硬化症患者的T细胞计数。

Long-term use of rituximab increases T cell count in MS patients.

作者信息

Björnsson Gunnar Sigfús, Sigurgrímsdóttir Hildur, Maggadóttir Sólrún Melkorka, Einarsdóttir Berglind Ósk, Sveinsson Ólafur Árni, Hjaltason Haukur, Sigurðardóttir Sigurveig Þóra, Lúðvíksson Björn Rúnar, Brynjólfsson Siggeir Fannar

机构信息

Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

Department of Immunology, Landspítali - The National University Hospital of Iceland, Reykjavik, Iceland.

出版信息

Front Immunol. 2024 Jul 17;15:1412668. doi: 10.3389/fimmu.2024.1412668. eCollection 2024.

Abstract

Rituximab has been used to treat MS patients in Iceland for over a decade. However, long-term effect of rituximab on leukocyte populations has not yet been elucidated. By retrospective analysis of flow cytometric data from 349 patients visiting the neurological ward at The National University Hospital of Iceland from 2012 to 2023 for rituximab treatment, the long-term effect of rituximab and whether the effect was dose dependent (1000mg vs 500mg) was evaluated. No difference was detected in efficacy of B cell depletion in patients treated with 500mg as an initial dose of rituximab when compared to 1000mg. Long-term use of rituximab led to an increase in T cell count (p=0,0015) in patients receiving 3-8 doses of rituximab (1.5-8 years of treatment). The increase occurred in both CD4 (p=0,0028) and CD8 T cells (p=0,0015) and led to a decrease in the CD4/CD8 ratio (p=0,004). The most notable difference lies in reshaping the balance between näive and effector CD8 T cells. The clinical implications of long-term treatment with rituximab and its effect on the T cell pool needs to be explored further. Since no difference in B cell depletion was detected between the two patient groups, 1000mg as an initial dose might be excessive, suggesting a personalized dosing regimen might have therapeutic and financial advantages.

摘要

利妥昔单抗在冰岛用于治疗多发性硬化症(MS)患者已有十多年。然而,利妥昔单抗对白细胞群体的长期影响尚未阐明。通过对2012年至2023年在冰岛国立大学医院神经科病房接受利妥昔单抗治疗的349例患者的流式细胞术数据进行回顾性分析,评估了利妥昔单抗的长期影响以及该影响是否具有剂量依赖性(1000mg与500mg)。与1000mg相比,以500mg作为利妥昔单抗初始剂量治疗的患者在B细胞耗竭疗效方面未检测到差异。在接受3 - 8剂利妥昔单抗治疗(治疗1.5 - 8年)的患者中,长期使用利妥昔单抗导致T细胞计数增加(p = 0.0015)。CD4(p = 0.0028)和CD8 T细胞(p = 0.0015)均出现增加,并导致CD4/CD8比值降低(p = 0.004)。最显著的差异在于重塑了幼稚型和效应型CD8 T细胞之间的平衡。利妥昔单抗长期治疗的临床意义及其对T细胞库的影响需要进一步探索。由于两组患者在B细胞耗竭方面未检测到差异,1000mg作为初始剂量可能过高,这表明个性化给药方案可能具有治疗和经济优势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8ad/11288840/f673a5b2ccc2/fimmu-15-1412668-g001.jpg

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