Autoantibodies and cell-mediated Autoimmunity to NMDA-type GluRε2 in patients with Rasmussen's encephalitis and chronic progressive epilepsia partialis continua
Autoantibodies and cell-mediated Autoimmunity to NMDA-type GluRε2 in patients with Rasmussen's encephalitis and chronic progressive epilepsia partialis continua
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DOI：
10.1111/j.1528-1167.2005.01024.x
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发表时间：
2005-01-01
期刊：
影响因子：
5.6
通讯作者：
Fujiwara, T
中科院分区：
文献类型：
--
作者：
Takahashi, Y;Mori, T;Fujiwara, T
目的：探讨抗体和细胞毒T细胞介导的自身免疫性在拉斯穆森脑炎发病机制中的作用。方法：检测20例患者血清和脑脊液中抗N-甲基-D-天冬氨酸受体(NMDA型GluR)2亚单位及其表位的自身抗体，其中5例经组织学证实的Rasmussen脑炎伴持续癫痫(EPC)，4例明确的Rasmussen脑炎不伴EPC，I例临床诊断为EPC的Rasmussen脑炎。结果：9例确诊患者(5例EPC患者和4例非EPC患者)和10例I I临床拉斯穆森脑炎患者均有自身抗体。在4例患者中，在癫痫发作已经频繁的早期，自身抗体缺失，随后出现自身抗体。在两名患者中，尽管癫痫发作得到完全控制，但额叶切除或功能性半球切除后血清中仍有自身抗体存在。针对C2表位的自身抗体占主导地位，而针对细胞外N表位的自身抗体很少。确诊Rasmussen脑炎患者和临床Rasmussen脑炎患者的平均H-3-胸腺嘧啶核苷摄取率(含Glur epsilon 2匀浆刺激/PHA刺激)显著高于对照组。含Glur epsilon 2匀浆的H-3-胸腺嘧啶核苷摄取率(相对于PHA)显著高于对照组和含Glur Delta 2匀浆。结论：抗Glur epsilon 2自身抗体可作为Rasmussen脑炎伴EPC和不伴EPC的诊断指标之一。患者在外周血液循环中被Glur epsilon 2刺激的T细胞激活。我们推测细胞自身免疫和随后针对Glur epsilon 2的体液自身免疫可能参与了Rasmussen脑炎的病理生理过程。
Purpose: To evaluate antibody-mediated and cytotoxic T cell-mediated pathogenicity that has been implicated as the autoimmune pathophysiological mechanism in Rasmussen's encephalitis.Methods: We examined autoantibodies against the N-methyl-D-aspartate glutamate receptor (NMDA-type GluR) epsilon 2 subunit and its epitopes in serum and CSF samples from 20 patients [five histologically proven (definitive) Rasmussen's encephalitis with epilepsia partialis continua (EPC), four definitive Rasmussen's encephalitis without EPC, and I I clinical Rasmussen's encephalitis with EPC]. We examined H-3-thymidine uptake into lymphocytes after stimulation by GluRs.Results: All nine definitive patients (five patients with EPC and four without EPC), and 10 of I I clinical Rasmussen's encephalitis patients had the autoantibodies. In four patients, the autoantibodies were absent in early stage when epileptic seizures had already become frequent, and appeared subsequently. In two patients, the autoantibodies persisted in the serum after frontal lobe resection or functional hemispherectomy, although epileptic seizures were completely controlled. Autoantibodies to the C2 epitope predominated, while autoantibodies to the extracellular N epitope were rare. The mean H-3-thymidine uptake ratios (stimulation by GluR epsilon 2-containing homogenates/stimulation by PHA) were significantly higher in definitive and clinical Rasmussen encephalitis patients than in controls. The mean H-3-thymidine uptake ratios (relative to PHA) were significantly higher for GluR epsilon 2-containing homogenate than for control hemogenate or GluR delta 2-containing homogenate.Conclusions: Autoantibodies against GluR epsilon 2 may be one of the diagnostic markers for Rasmussen's encephalitis with and without EPC. Patients have activated T cells stimulated by GluR epsilon 2 in peripheral blood circulation. We speculate that cellular autoimmunity and the subsequent humoral autoimmunity against GluR epsilon 2 may contribute to the pathophysiological processes in Rasmussen's encephalitis.