Long-term modifications of the peripheral immune repertoire after switching from sequestering disease-modifying treatments in multiple sclerosis.

IF 4.8 2区 医学 Q1 CLINICAL NEUROLOGY
Marco Vercellino, Stella Marasciulo, Emanuela Ricotti, Anna Rolando, Chiara Bosa, Paola Garelli, Virginia Gallina, Giovanna Vaula, Andrea Calvo, Paola Cavalla
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Abstract

Background: Scarce data are available on the long-term immunological effects of multiple sclerosis (MS) disease-modifying treatments (DMTs).

Objectives: This study aimed to investigate the long-term modifications of the peripheral immune repertoire on interruption of a sequestering DMT (natalizumab, fingolimod) and switch to another high-efficacy DMT.

Methods: Lymphocyte subpopulations were assessed, every 6 months up to 48 months, in patients switched from fingolimod or natalizumab to ocrelizumab, and in patients switched from fingolimod to natalizumab, compared to patients switched to ocrelizumab or natalizumab from a moderate-efficacy DMT and to naive patients.

Results: We included 389 MS patients (200 ocrelizumab and 189 natalizumab). After adjusting for baseline variables, patients switched from fingolimod to ocrelizumab showed lower CD3 + and CD4 + lymphocytes up to 48 months after switch (with lower percentage of naive CD4 +), and increased odds of total, CD3+, CD4+ lymphopenia. Patients switched from natalizumab to ocrelizumab showed higher CD3 + lymphocytes up to 36 months after switch, and higher CD4+, CD8+ lymphocytes up to 24 months. The frequency of infections was not influenced by previous treatment.

Conclusions: A long-term persistence of the residual effects of the exposure to sequestering DMTs (fingolimod and less natalizumab) on the peripheral immune repertoire was observed after switching to another high-efficacy DMT.

多发性硬化症患者改用封存性疾病修饰疗法后外周免疫系统的长期改变。
背景有关多发性硬化症(MS)疾病修饰治疗(DMTs)的长期免疫学效应的数据十分稀少:本研究旨在调查在中断一种封闭性DMT(纳他珠单抗、芬戈莫德)并改用另一种高效DMT治疗后,外周免疫细胞群的长期变化情况:结果:我们纳入了389名多发性硬化症患者(200名),其中包括从芬戈莫德或纳妥珠单抗转为奥柯利珠单抗的患者,以及从芬戈莫德转为纳妥珠单抗的患者:我们共纳入了 389 名多发性硬化症患者(其中 200 名是奥柯利珠单抗患者,189 名是纳他珠单抗患者)。在对基线变量进行调整后,从芬戈莫德转为奥克雷珠单抗的患者在转药后48个月内的CD3+和CD4+淋巴细胞均较低(幼稚CD4+的比例较低),总淋巴细胞、CD3+、CD4+淋巴细胞减少的几率增加。从纳他珠单抗转为奥克雷珠单抗的患者在转药后36个月内CD3+淋巴细胞较高,24个月内CD4+、CD8+淋巴细胞较高。感染频率不受先前治疗的影响:结论:在改用另一种高效DMT治疗后,观察到暴露于螯合DMT(芬戈莫德和较少的纳他珠单抗)对外周免疫复合物的残余效应长期存在。
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来源期刊
Multiple Sclerosis Journal
Multiple Sclerosis Journal 医学-临床神经学
CiteScore
10.90
自引率
6.90%
发文量
186
审稿时长
3-8 weeks
期刊介绍: Multiple Sclerosis Journal is a peer-reviewed international journal that focuses on all aspects of multiple sclerosis, neuromyelitis optica and other related autoimmune diseases of the central nervous system. The journal for your research in the following areas: * __Biologic basis:__ pathology, myelin biology, pathophysiology of the blood/brain barrier, axo-glial pathobiology, remyelination, virology and microbiome, immunology, proteomics * __Epidemology and genetics:__ genetics epigenetics, epidemiology * __Clinical and Neuroimaging:__ clinical neurology, biomarkers, neuroimaging and clinical outcome measures * __Therapeutics and rehabilitation:__ therapeutics, rehabilitation, psychology, neuroplasticity, neuroprotection, and systematic management Print ISSN: 1352-4585
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