抗N-甲基-D-天门冬氨酸受体脑炎发病机制的研究进展

刘梦佳; 邹丽萍

doi:10.7499/j.issn.1008-8830.2014.06.002

PDF(962 KB)

HTML

中国当代儿科杂志 ›› 2014, Vol. 16 ›› Issue (6) : 571-574. DOI: 10.7499/j.issn.1008-8830.2014.06.002

抗NMDAR脑炎专题

抗N-甲基-D-天门冬氨酸受体脑炎发病机制的研究进展

刘梦佳, 邹丽萍

作者信息 +

Research advances in pathogenesis of anti-N-methyl-D-aspartate receptor encephalitis

LIU Meng-Jia, ZOU Li-Ping

Author information +

Children's Medical Center, General Hospital of People's Liberation Army, Beijing 100853, China

Aboat authors:

[1] Gable MS, Sheriff H, Dalmau J, et al. The frequency of autoimmune N-methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project [J].Clin Infect Diseases, 2012, 54(7): 899-904.
[2] Titulaer MJ, Mccracken L, Gabilondo I, et al. Treatment and prognostic factors for long-term outcome in patients with anti- NMDA receptor encephalitis: an observational cohort study [J].Chin J Contemp Pediatr Lancet Neurol, 2013, 12(2): 157-165.
[3] Vitaliani R, Mason W, Ances B, et al. Paraneoplastic encephalitis, psychiatric symptoms, and hypoventilation in ovarian teratoma[J].Ann Neurol, 2005, 58(4): 594-604.
[4] Dalmau J, Tüzün E, Wu HY, et al. Paraneoplastic anti-Nmethyl- D-aspartate receptor encephalitis associated with ovarian teratoma[J].Ann Neurol, 2007, 61(1): 25-36.
[5] Mangler M, Trebesch de Perez I, Teegen B, et al. Seroprevalence of anti-N-methyl-D-aspartate receptor antibodies in women with ovarian teratoma[J].J Neurol, 2013, 260(11): 2831-2835.
[6] Seki M, Suzuki S, Iizuka T, et al. Neurological response to early removal of ovarian teratoma in anti-NMDAR encephalitis[J].J Neurol Neurosurg Psychiatry, 2008, 79(3): 324-326.
[7] Dalmau J, Gleichman AJ, Hughes EG, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies [J].Lancet Neurol, 2008, 7(12): 1091-1098.
[8] Tuzun E, Zhou L, Baehring JM, et al. Evidence for antibodymediated pathogenesis in anti-NMDAR encephalitis associated with ovarian teratoma [J].Acta Neuropathol, 2009, 118(6): 737- 743.
[9] Dabner M, Mccluggage WG, Bundell C, et al. Ovarian teratoma associated with anti-N-methyl D-aspartate receptor encephalitis: a report of 5 cases documenting prominent intratumoral lymphoid infiltrates [J].Int J Gynecol Pathol, 2012, 31(5): 429-437.
[10] Bien CG, Vincent A, Barnett MH, et al. Immunopathology of autoantibody-associated encephalitides: clues for pathogenesis [J].Brain, 2012, 135(Pt 5): 1622-1638.
[11] Irani SR, Bera K, Waters P, et al. N-methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes [J].Brain, 2010, 133(Pt 6): 1655-1667.
[12] Camdessanche JP, Streichenberger N, Cavillon G, et al. Brain immunohistopathological study in a patient with anti-NMDAR encephalitis [J].Europ J Neurol, 2011, 18(6): 929-931.
[13] Martinez-Hernandez E, Horvath J, Shiloh-Malawsky Y, et al. Analysis of complement and plasma cells in the brain of patients with anti-NMDAR encephalitis [J].Neurology, 2011, 77(6): 589- 593.
[14] Hughes EG, Peng X, Gleichman AJ, et al. Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis [J].J Neurosci, 2010, 30(17): 5866-5875.
[15] Mikasova L, De R0ssi P, Bouchet D, et al. Disrupted surface cross-talk between NMDA and Ephrin-B2 receptors in anti- NMDA encephalitis [J].Brain, 2012, 135(Pt 5): 1606-1621.
[16] Dulcey I, Cespedes MU, Ballesteros JL, et al. Necrotic mature ovarian teratoma associated with anti-N-methyl-D-aspartate receptor encephalitis [J].Pathol Res Pract, 2012, 208(8): 497-500.
[17] Peery HE, Day GS, Dunn S, et al. Anti-NMDA receptor encephalitis. The disorder, the diagnosis and the immunobiology[J].Autoimm Rev, 2012, 11(12): 863-872.

Show less

文章历史 +

摘要

抗N-甲基-D-天门冬氨酸受体（NMDAR）脑炎已经成为脑炎疾病当中最主要的类型。阐明抗NMDAR 脑炎的发病机制对于理解该病，进而进行合理的治疗是非常有必要的。该文从以下几个方面进行综述：（1）抗NMDAR 脑炎发病与肿瘤关系的发现；（2）抗NMDAR 脑炎与肿瘤关系的进一步研究；（3）抗NMDAR 抗体识别的抗原决定部位，患者的自身免疫反应；（4）抗体与受体的作用：（5）不伴有肿瘤的抗NMDAR 脑炎的发病机制。该文向读者展示了这个病从在临床中被发现，到认识它和肿瘤的关系，再到从病理组织、分子水平以及信号传导水平进行研究的过程。展现一个科研思路，告诉读者临床医生是如何在临床中发现问题并逐步深入解决问题。目前的研究已证明抗NMDAR 脑炎是一种和肿瘤尤其是卵巢畸胎瘤密切相关的神经系统自身免疫性疾病。

Abstract

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most prevalent type of encephalitis. Investigating the pathogenesis of anti-NMDAR encephalitis will enhance our understanding of this disease and play a central part in providing reasonable treatment for the patients. The pathogenesis is elucidated as follows: (1) the findings of the relationship between anti-NMDAR encephalitis and tumors; (2) further research on the relationship between anti-NMDAR encephalitis and tumors; (3) NMDAR epitopes and the autoimmunity of patients; (4) the interaction between antibody and NMDAR; (5) the pathogenesis of anti-NMDAR encephalitis without tumors. This review gives a brief introduction to the methodology and way of finding out the valuable clinical problems and making a clear and explicit explanation of them by exhibiting the process of discovering the disease, disclosing its relationship with tumors, and investigating its pathological and molecular mechanism. Current studies have demonstrated that anti-NMDAR encephalitis is an autoimmune disease of the nervous system that is closely associated with tumors, particularly ovarian teratoma.

导出引用

刘梦佳, 邹丽萍. 抗N-甲基-D-天门冬氨酸受体脑炎发病机制的研究进展[J]. 中国当代儿科杂志. 2014, 16(6): 571-574 https://doi.org/10.7499/j.issn.1008-8830.2014.06.002

LIU Meng-Jia, ZOU Li-Ping. Research advances in pathogenesis of anti-N-methyl-D-aspartate receptor encephalitis[J]. Chinese Journal of Contemporary Pediatrics. 2014, 16(6): 571-574 https://doi.org/10.7499/j.issn.1008-8830.2014.06.002