B 细胞在多发性硬化症中的作用：当前和未来的治疗方法。
The role of B cells in multiple sclerosis: Current and future therapies.
机构信息
Department of Biology, University of Texas at San Antonio, TX 78249, USA.
Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA; Neurology Section, VA North Texas Health Care System, Medical Service, Dallas, TX, USA.
出版信息
Cell Immunol. 2019 May;339:10-23. doi: 10.1016/j.cellimm.2018.10.006. Epub 2018 Oct 21.
Abstract
While it was long held that T cells were the primary mediators of multiple sclerosis (MS) pathogenesis, the beneficial effects observed in response to treatment with Rituximab (RTX), a monoclonal antibody (mAb) targeting CD20, shed light on a key contributor to MS that had been previously underappreciated: B cells. This has been reaffirmed by results from clinical trials testing the efficacy of subsequently developed B cell-depleting mAbs targeting CD20 as well as studies revisiting the effects of previous disease-modifying therapies (DMTs) on B cell subsets thought to modulate disease severity. In this review, we summarize current knowledge regarding the complex roles of B cells in MS pathogenesis and current and potential future B cell-directed therapies.
摘要
虽然长期以来人们一直认为 T 细胞是多发性硬化症 (MS) 发病机制的主要介质，但利妥昔单抗（RTX）治疗的疗效观察表明，B 细胞是 MS 的一个此前被低估的关键贡献者，RTX 是一种针对 CD20 的单克隆抗体。随后针对 CD20 的 B 细胞耗竭单克隆抗体的临床试验结果以及重新研究先前改变疾病疗法 (DMT) 对被认为调节疾病严重程度的 B 细胞亚群的影响的研究进一步证实了这一点。在这篇综述中，我们总结了目前关于 B 细胞在 MS 发病机制中的复杂作用以及当前和潜在的未来 B 细胞靶向治疗的知识。
相似文献
1
The role of B cells in multiple sclerosis: Current and future therapies.
Cell Immunol. 2019 May;339:10-23. doi: 10.1016/j.cellimm.2018.10.006. Epub 2018 Oct 21.
2
Anti-CD20 Monoclonal Antibodies for Relapsing and Progressive Multiple Sclerosis.
CNS Drugs. 2020 Mar;34(3):269-280. doi: 10.1007/s40263-020-00704-w.
3
Therapies for multiple sclerosis targeting B cells.
Croat Med J. 2019 Apr 30;60(2):87-98. doi: 10.3325/cmj.2019.60.87.
4
A Milestone in Multiple Sclerosis Therapy: Monoclonal Antibodies Against CD20-Yet Progress Continues.
Neurotherapeutics. 2021 Jul;18(3):1602-1622. doi: 10.1007/s13311-021-01048-z. Epub 2021 Apr 20.
5
CD20 monoclonal antibodies for the treatment of multiple sclerosis: up-to-date.
Expert Opin Biol Ther. 2019 Aug;19(8):829-843. doi: 10.1080/14712598.2019.1611778. Epub 2019 May 24.
6
Rituximab efficiently depletes increased CD20-expressing T cells in multiple sclerosis patients.
J Immunol. 2014 Jul 15;193(2):580-586. doi: 10.4049/jimmunol.1400118. Epub 2014 Jun 13.
7
B cell-directed therapies in multiple sclerosis.
Neurodegener Dis Manag. 2016;6(1):37-47. doi: 10.2217/nmt.15.67.
8
Binding of submaximal C1q promotes complement-dependent cytotoxicity (CDC) of B cells opsonized with anti-CD20 mAbs ofatumumab (OFA) or rituximab (RTX): considerably higher levels of CDC are induced by OFA than by RTX.
J Immunol. 2009 Jul 1;183(1):749-58. doi: 10.4049/jimmunol.0900632. Epub 2009 Jun 17.
9
Treatment of multiple sclerosis with anti-CD20 antibodies.
Clin Immunol. 2012 Jan;142(1):31-7. doi: 10.1016/j.clim.2011.04.005. Epub 2011 Apr 15.
10
The different clinical effects of anti-BLyS, anti-APRIL and anti-CD20 antibodies point at a critical pathogenic role of γ-herpesvirus infected B cells in the marmoset EAE model.
J Neuroimmune Pharmacol. 2013 Jun;8(3):727-38. doi: 10.1007/s11481-013-9448-6. Epub 2013 Mar 19.
引用本文的文献
1
Overtime Challenges of Diagnosis and Treatment in Two Pediatric Patients with Extensive Cerebral Tumefactive Lesions Indicative of Baló's Type Multiple Sclerosis.
Children (Basel). 2025 May 14;12(5):630. doi: 10.3390/children12050630.
2
Mesenchymal stem cells and their derived exosomes in multiple sclerosis disease: from paper to practice.
Mol Cell Biochem. 2024 Jul;479(7):1643-1671. doi: 10.1007/s11010-024-05051-8. Epub 2024 Jul 8.
3
Mitochondrial and metabolic dysfunction of peripheral immune cells in multiple sclerosis.
J Neuroinflammation. 2024 Jan 20;21(1):28. doi: 10.1186/s12974-024-03016-8.
4
Repeated iv anti-CD20 treatment in multiple sclerosis: Long-term effects on peripheral immune cell subsets.
Ann Clin Transl Neurol. 2024 Feb;11(2):450-465. doi: 10.1002/acn3.51965. Epub 2024 Jan 10.
5
Key characteristics of anti-CD20 monoclonal antibodies and clinical implications for multiple sclerosis treatment.
J Neurol. 2024 Apr;271(4):1515-1535. doi: 10.1007/s00415-023-12007-3. Epub 2023 Oct 31.
6
Patient and nurse preference for Sensoready autoinjector pen versus other autoinjectors in multiple sclerosis: results from a pilot multicenter survey.
BMC Neurol. 2023 Feb 27;23(1):85. doi: 10.1186/s12883-023-03100-1.
7
From bedside to bench: how existing therapies inform the relationship between Epstein-Barr virus and multiple sclerosis.
Clin Transl Immunology. 2023 Feb 23;12(2):e1437. doi: 10.1002/cti2.1437. eCollection 2023.
8
Immunoregulation via Cell Density and Quorum Sensing-like Mechanisms: An Underexplored Emerging Field with Potential Translational Implications.
Cells. 2022 Aug 6;11(15):2442. doi: 10.3390/cells11152442.
9
Dissection of multiple sclerosis genetics identifies B and CD4+ T cells as driver cell subsets.
Genome Biol. 2022 Jun 7;23(1):127. doi: 10.1186/s13059-022-02694-y.
10
Prioritization of autoimmune disease-associated genetic variants that perturb regulatory element activity in T cells.
Nat Genet. 2022 May;54(5):603-612. doi: 10.1038/s41588-022-01056-5. Epub 2022 May 5.
本文引用的文献
1
Granulocyte-macrophage colony-stimulating factor as a mediator of autoimmunity in multiple sclerosis.
J Neuroimmunol. 2018 Oct 15;323:1-9. doi: 10.1016/j.jneuroim.2018.07.002. Epub 2018 Jul 5.
2
Cladribine: Off-label disease modification for people with multiple sclerosis in resource-poor settings?
Mult Scler J Exp Transl Clin. 2018 Jun 26;4(2):2055217318783767. doi: 10.1177/2055217318783767. eCollection 2018 Apr-Jun.
3
Reassessing B cell contributions in multiple sclerosis.
Nat Immunol. 2018 Jul;19(7):696-707. doi: 10.1038/s41590-018-0135-x. Epub 2018 Jun 20.
4
Targeting B Cells and Plasma Cells in Autoimmune Diseases.
Front Immunol. 2018 Apr 23;9:835. doi: 10.3389/fimmu.2018.00835. eCollection 2018.
5
Integrative analysis reveals CD38 as a therapeutic target for plasma cell-rich pre-disease and established rheumatoid arthritis and systemic lupus erythematosus.
Arthritis Res Ther. 2018 May 2;20(1):85. doi: 10.1186/s13075-018-1578-z.
6
B Cell Modulation Strategies in Autoimmune Diseases: New Concepts.
Front Immunol. 2018 Apr 13;9:622. doi: 10.3389/fimmu.2018.00622. eCollection 2018.
7
The Multiple Roles of B Cells in Multiple Sclerosis and Their Implications in Multiple Sclerosis Therapies.
Cold Spring Harb Perspect Med. 2019 Apr 1;9(4):a029108. doi: 10.1101/cshperspect.a029108.
8
B cell-based therapies in CNS autoimmunity: differentiating CD19 and CD20 as therapeutic targets.
Ther Adv Neurol Disord. 2018 Mar 21;11:1756286418761697. doi: 10.1177/1756286418761697. eCollection 2018.
9
Cladribine treatment of multiple sclerosis is associated with depletion of memory B cells.
J Neurol. 2018 May;265(5):1199-1209. doi: 10.1007/s00415-018-8830-y. Epub 2018 Mar 17.
10
MS drug is suspended after reports of inflammatory brain disorders.
BMJ. 2018 Mar 8;360:k1114. doi: 10.1136/bmj.k1114.
Zotero 插件