利妥昔单抗在抗MuSK抗体阳性重症肌无力中的应用进展

doi:10.3969/j.issn.1672-6731.2020.01.008

摘要/Abstract

摘要：

重症肌无力是一种自身抗体介导的针对神经肌肉接头突触后膜的自身免疫性疾病，抗肌肉特异性受体酪氨酸激酶（MuSK）抗体阳性（MuSK-MG）患者占所有重症肌无力患者的5%~8%。与抗乙酰胆碱受体（AChR）抗体阳性和血清抗AChR和MuSK抗体阴性患者相比，MuSK-MG患者发病时间早、病情严重、应用传统治疗不能有效控制疾病进展。利妥昔单抗是通过基因重组技术研制的针对B细胞表面CD20抗原的人鼠嵌合型单克隆抗体，可以有效治疗难治性重症肌无力，减少复发和肌无力危象次数，对难治性MuSK-MG患者具有良好的有效性和安全性。

关键词: 重症肌无力, 肌肉特异性受体酪氨酸激酶（非MeSH词）, 利妥昔单抗, 综述

Abstract:

Myasthenia gravis (MG) is an autoantibody mediated autoimmune disease of the neuromuscular junction (NMJ), and anti-muscle-specific receptor tyrosine kinase (MuSK) antibody-related MG (MuSK-MG) covers 5%-8% of all MG patients. MuSK-MG is a life threatening condition, characterized with early bulbar, neck, and respiratory muscle weakness. MuSK-MG patients have poor response to standard therapies, known as drug-resistant patients. Rituximab (RTX) is a monoclonal antibody that targets the CD20 antigen on B cells. At present, most studies have described clinical improvement and immunosuppressant dose reduction following RTX treatment of refractory MG patients, especially for MuSK-MG patients.

Key words: Myasthenia gravis, Muscle-specific receptor tyrosine kinase (not in MeSH), Rituximab, Review

李婷, 杨丽. 利妥昔单抗在抗MuSK抗体阳性重症肌无力中的应用进展[J]. 中国现代神经疾病杂志, 2020, 20(1): 48-54.

LI Ting, YANG Li. Progress in rituximab for anti-MuSK antibody-related myasthenia gravis[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2020, 20(1): 48-54.

http://journal11.magtechjournal.com/cjcnn/CN/Y2020/V20/I1/48

参考文献

[1] Gilhus NE, Tzartos S, Evoli A, Palace J, Burns TM, Verschuuren JJ. Myasthenia gravis[J]. Nat Rev Dis Primers, 2019, 5:30.
[2] Salles G, Barrett M, Foà R, Maurer J, O'Brien S, Valente N, Wenger M, Maloney DG. Rituximab in B-cell hematologic malignancies:a review of 20 years of clinical experience[J]. Adv Ther, 2017, 34:2232-2273.
[3] Einarsson JT, Evert M, Geborek P, Saxne T, Lundgren M, Kapetanovic MC. Rituximab in clinical practice:dosage, drug adherence, Ig levels, infections, and drug antibodies[J]. Clin Rheumatol, 2017, 36:2743-2750.
[4] Hui-Yuen JS, Nguyen SC, Askanase AD. Targeted B cell therapies in the treatment of adult and pediatric systemic lupus erythematosus[J]. Lupus, 2016, 25:1086-1096.
[5] Grace RF, Shimano KA, Bhat R, Neunert C, Bussel JB, Klaassen RJ, Lambert MP, Rothman JA, Breakey VR, Hege K, Bennett CM, Rose MJ, Haley KM, Buchanan GR, Geddis A, Lorenzana A, Jeng M, Pastore YD, Crary SE, Neier M, Neufeld EJ, Neu N, Forbes PW, Despotovic JM. Second-line treatments in children with immune thrombocytopenia:effect on platelet count and patient-centered outcomes[J]. Am J Hematol, 2019, 94:741-750.
[6] Dalakas MC. Immunotherapy in myasthenia gravis in the era of biologics[J]. Nat Rev Neurol, 2019, 15:113-124.
[7] Robeson KR, Kumar A, Keung B, DiCapua DB, Grodinsky E, Patwa HS, Stathopoulos PA, Goldstein JM, O'Connor KC, Nowak RJ. Durability of the rituximab response in acetylcholine receptor autoantibody-positive myasthenia gravis[J]. JAMA Neurol, 2017, 74:60-66.
[8] Yi JS, Guptill JT, Stathopoulos P, Nowak RJ, O'Connor KC. B cells in the pathophysiology of myasthenia gravis[J]. Muscle Nerve, 2018, 57:172-184.
[9] Phillips WD, Vincent A. Pathogenesis of myasthenia gravis:update on disease types, models, and mechanisms[J]. F1000Res, 2016, 5 pii:1513.
[10] Koneczny I, Stevens JA, De Rosa A, Huda S, Huijbers MG, Saxena A, Maestri M, Lazaridis K, Zisimopoulou P, Tzartos S, Verschuuren J, van der Maarel SM, van Damme P, De Baets MH, Molenaar PC, Vincent A, Ricciardi R, Martinez-Martinez P, Losen M. IgG4 autoantibodies against muscle-specific kinase undergo Fab-arm exchange in myasthenia gravis patients[J]. J Autoimmun, 2017, 77:104-115.
[11] Stathopoulos P, Kumar A, Heiden JA, Pascual-Goñi E, Nowak RJ, O'Connor KC. Mechanisms underlying B cell immune dysregulation and autoantibody production in MuSK myasthenia gravis[J]. Ann NY Acad Sci, 2018, 1412:154-165.
[12] Vander Heiden JA, Stathopoulos P, Zhou JQ, Chen L, Gilbert TJ, Bolen CR, Barohn RJ, Dimachkie MM, Ciafaloni E, Broering TJ, Vigneault F, Nowak RJ, Kleinstein SH, O'Connor KC. Dysregulation of b cell repertoire formation in myasthenia gravis patients revealed through deep sequencing[J]. J Immunol, 2017, 198:1460-1473.
[13] Ramwadhdoebe TH, van Baarsen LG, Boumans MJ, Bruijnen ST, Safy M, Berger FH, Semmelink JF, van der Laken CJ, Gerlag DM, Thurlings RM, Tak PP. Effect of rituximab treatment on T and B cell subsets in lymph node biopsies of patients with rheumatoid arthritis[J]. Rheumatology (Oxford), 2019, 58:1075-1085.
[14] Illa I, Diaz-Manera J, Rojas-Garcia R, Pradas J, Rey A, Blesa R, Juarez C, Gallardo E. Sustained response to rituximab in anti-AChR and anti-MuSK positive myasthenia gravis patients[J]. J Neuroimmunol, 2008, 201/202:90-94.
[15] Blum S, Gillis D, Brown H, Boyle R, Henderson R, Heyworth-Smith D, Hogan P, Kubler P, Lander C, Limberg N, Pillans P, Prain K, Staples C, Walsh M, McCombe P, Wong R. Use and monitoring of low dose rituximab in myasthenia gravis[J]. J Neurol Neurosurg Psychiatry, 2011, 82:659-663.
[16] Díaz-Manera J, Martínez-Hernández E, Querol L, Klooster R, Rojas-García R, Suárez-Calvet X, Muñ oz-Blanco JL, Mazia C, Straasheijm KR, Gallardo E, Juárez C, Verschuuren JJ, Illa I. Long-lasting treatment effect of rituximab in MuSK myasthenia[J]. Neurology, 2012, 78:189-193.
[17] Huang H, Benoist C, Mathis D. Rituximab specifically depletes short-lived autoreactive plasma cells in a mouse model of inflammatory arthritis[J]. Proc Natl Acad Sci USA, 2010, 107:4658-4663.
[18] Winter O, Dame C, Jundt F, Hiepe F. Pathogenic long-lived plasma cells their survival niches in autoimmunity, malignancy, and allergy[J]. J Immunol, 2012, 189:5105-5111.
[19] Keung B, Robeson KR, DiCapua DB, Rosen JB, O'Connor KC, Goldstein JM, Nowak RJ. Long-term benefit of rituximab in MuSK autoantibody myasthenia gravis patients[J]. J Neurol Neurosurg Psychiatry, 2013, 84:1407-1409.
[20] Anderson D, Phan C, Johnston WS, Siddiqi ZA. Rituximab in refractory myasthenia gravis:a prospective, open-label study with long-term follow-up[J]. Ann Clin Transl Neurol, 2016, 3:552-555.
[21] Afanasiev V, Demeret S, Bolgert F, Eymard B, Laforêt P, Benveniste O. Resistant myasthenia gravis and rituximab:a monocentric retrospective study of 28 patients[J]. Neuromuscul Disord, 2017, 27:251-258.
[22] Hehir MK, Hobson-Webb LD, Benatar M, Barnett C, Silvestri NJ, Howard JF Jr, Howard D, Visser A, Crum BA, Nowak R, Beekman R, Kumar A, Ruzhansky K, Chen IA, Pulley MT, LaBoy SM, Fellman MA, Greene SM, Pasnoor M, Burns TM. Rituximab as treatment for anti-MuSK myasthenia gravis:multicenter blinded prospective review[J]. Neurology, 2017, 89:1069-1077.
[23] Beecher G, Anderson D, Siddiqi ZA. Rituximab in refractory myasthenia gravis:extended prospective study results[J]. Muscle Nerve, 2018, 58:452-455.
[24] Chan F, Swayne A, Gillis D, Walsh M, Henderson RD, Mc Combe PA, Wong RC, Blum S. Long-term follow-up of patients with myasthenia gravis treated with low-dose rituximab[J]. J Neurol Neurosurg Psychiatry, 2019, 90:955-956.
[25] Topakian R, Zimprich F, Iglseder S, Embacher N, Guger M, Stieglbauer K, Langenscheidt D, Rath J, Quasthoff S, Simschitz P, Wanschitz J, Windisch D, Müller P, Oel D, Schustereder G, Einsiedler S, Eggers C, L öscher W. High efficacy of rituximab for myasthenia gravis:a comprehensive nationwide study in Austria[J]. J Neurol, 2019, 266:699-706.
[26] Kanth KM, Solorzano GE, Goldman MD. PML in a patient with myasthenia gravis treated with multiple immunosuppressing agents[J]. Neurol Clin Pract, 2016, 6:E17-19.
[27] Strand V, Balsa A, Al-Saleh J, Barile-Fabris L, Horiuchi T, Takeuchi T, Lula S, Hawes C, Kola B, Marshall L. Immunogenicity of biologics in chronic in flammatory diseases:a systematic review[J]. BioDrugs, 2017, 31:299-316.
[28] Md Yusof MY, Shaw D, El-Sherbiny YM, Dunn E, Rawstron AC, Emery P, Vital EM. Predicting and managing primary and secondary non-response to rituximab using B-cell biomarkers in systemic lupus erythematosus[J]. Ann Rheum Dis, 2017, 76:1829-1836.
[29] Dunn N, Juto A, Ryner M, Manouchehrinia A, Piccoli L, Fink K, Piehl F, Fogdell-Hahn A. Rituximab in multiple sclerosis:frequency and clinical relevance of anti-drug antibodies[J]. Mult Scler, 2018, 24:1224-1233.
[30] Li T, Zhang LJ, Zhang QX, Yang CS, Zhang C, Li YJ, Shi FD, Yang L. Anti-Rituximab antibody in patients with NMOSDs treated with low dose Rituximab[J]. J Neuroimmunol, 2018, 316:107-111.

选择文件类型/文献管理软件名称

选择包含的内容

2 利妥昔单抗在抗MuSK抗体阳性重症肌无力中的应用进展

Progress in rituximab for anti-MuSK antibody-related myasthenia gravis

RichHTML

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	薛蓉, 张轩. 睡眠障碍对脑血管病的影响[J]. 中国现代神经疾病杂志, 2023, 23(8): 659-662.
[2]	张鹏, 陈涛, 许莉. 成人失眠认知行为疗法关键技术与流程改进建议[J]. 中国现代神经疾病杂志, 2023, 23(8): 663-667.
[3]	张轩, 薛蓉. 特发性快速眼动睡眠期行为障碍向神经系统变性疾病转化的生物学标志物研究进展[J]. 中国现代神经疾病杂志, 2023, 23(8): 668-673.
[4]	刘引, 汤永红, 翟锦霞, 邱媛. 慢性低度炎症与睡眠障碍研究进展[J]. 中国现代神经疾病杂志, 2023, 23(8): 674-677.
[5]	于洁洋, 张亚男, 李惠敏, 黄真灿, 李宛儒, 王赞. 发作性睡病与焦虑研究进展[J]. 中国现代神经疾病杂志, 2023, 23(8): 678-682.
[6]	库成心, 邓丽影, 谢亮. 缺血性卒中继发日间过度思睡研究进展[J]. 中国现代神经疾病杂志, 2023, 23(8): 683-686.
[7]	姜佳凤, 赵莲花, 赵伟. 褪黑素在阿尔茨海默病病理损害机制中的作用[J]. 中国现代神经疾病杂志, 2023, 23(8): 687-692.
[8]	黄沛, 王刚. 功能性帕金森综合征诊断与治疗[J]. 中国现代神经疾病杂志, 2023, 23(8): 738-741.
[9]	洪涛, 唐斌. 如何成为一名优秀的颅底外科医师[J]. 中国现代神经疾病杂志, 2023, 23(7): 571-574.
[10]	张庆硕, 宋丹丹, 周世越, 张金璐, 韩晓旭, 许顺良. 功能性步态障碍诊断与治疗[J]. 中国现代神经疾病杂志, 2023, 23(7): 604-609.
[11]	潘希娟, 邢英琦, 刘玉梅. 脑小血管病影像学评分方法[J]. 中国现代神经疾病杂志, 2023, 23(7): 633-637.
[12]	俞淑凤, 李宁, 徐健, 王鹏. 颈动脉漂浮血栓相关缺血性卒中诊断与治疗进展[J]. 中国现代神经疾病杂志, 2023, 23(7): 638-642.
[13]	魏俊吉. 神经外科重症医学规范化诊断与治疗[J]. 中国现代神经疾病杂志, 2023, 23(6): 477-478.
[14]	杜倩, 邓素君, 邹姗, 金珺, 周青山. 宏基因组第二代测序技术在重症中枢神经系统感染中的应用[J]. 中国现代神经疾病杂志, 2023, 23(6): 479-484.
[15]	曲鑫, 赵浩, 尚峰, 王宁. 神经重症目标温度管理[J]. 中国现代神经疾病杂志, 2023, 23(6): 485-489.

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

2 利妥昔单抗在抗MuSK抗体阳性重症肌无力中的应用进展

Progress in rituximab for anti-MuSK antibody-related myasthenia gravis

RichHTML

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价