Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen.
Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen.
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DOI：
10.1016/s1474-4422(09)70324-2
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发表时间：
2010-01
期刊：
影响因子：
48
通讯作者：
Dalmau, Josep
中科院分区：
文献类型：
--
作者：
Lancaster, Eric;Lai, Meizan;Peng, Xiaoyu;Hughes, Ethan;Constantinescu, Radu;Raizer, Jeffrey;Friedman, Daniel;Skeen, Mark B.;Grisold, Wolfgang;Kimura, Akio;Ohta, Kouichi;Iizuka, Takahiro;Guzman, Miguel;Graus, Francesc;Moss, Stephen J.;Balice-Gordon, Rita;Dalmau, Josep
一些脑炎或癫痫发作疾病曾经被认为是自发性的，现在似乎是免疫介导的。我们的目的是描述一个这样的疾病的临床特点，并确定涉及的自身抗原。对15例疑似副肿瘤性或免疫介导的边缘叶脑炎患者进行临床评估。共聚焦显微镜、免疫沉淀和质谱法用于鉴定自身抗原。使用啮齿动物GABAB 1或GABAB 2受体亚基转染的HEK 293细胞的测定作为血清学试验。91例疑似副肿瘤性或免疫介导的脑炎患者和13例谷氨酸脱羧酶65抗体相关综合征患者作为对照。所有患者均出现早期或显著癫痫发作;其他症状、MRI和脑电图结果与主要边缘功能障碍一致。所有患者都有针对神经元细胞表面抗原的抗体（主要是IgG 1）; 3例患者仅在CSF中检测到抗体。免疫沉淀和质谱分析表明，抗体识别GABAB受体的B1亚基，GABAB受体是一种抑制性受体，在被破坏时与癫痫发作和记忆功能障碍有关。共聚焦显微镜显示抗体与GABAB受体的共定位。15名患者中有7名患有肿瘤，其中5名为小细胞肺癌，7名患者患有非神经元自身抗体。虽然接受免疫治疗和癌症治疗（当发现肿瘤时）的10名患者中有9名显示神经系统改善，但没有接受类似治疗的4名患者中没有一名改善（p=0.005）。在104名对照中的两名中鉴定出低水平的GABAB 1受体抗体（p<0.0001）。GABAB受体自身免疫性脑炎是一种以癫痫发作为特征的潜在可治疗疾病，在某些患者中，与小细胞肺癌和其他自身抗体相关。国立卫生研究院。
Some encephalitides or seizure disorders once thought idiopathic now seem to be immune mediated. We aimed to describe the clinical features of one such disorder and to identify the autoantigen involved. 15 patients who were suspected to have paraneoplastic or immune-mediated limbic encephalitis were clinically assessed. Confocal microscopy, immunoprecipitation, and mass spectrometry were used to characterise the autoantigen. An assay of HEK293 cells transfected with rodent GABAB1 or GABAB2 receptor subunits was used as a serological test. 91 patients with encephalitis suspected to be paraneoplastic or immune mediated and 13 individuals with syndromes associated with antibodies to glutamic acid decarboxylase 65 were used as controls. All patients presented with early or prominent seizures; other symptoms, MRI, and electroencephalography findings were consistent with predominant limbic dysfunction. All patients had antibodies (mainly IgG1) against a neuronal cell-surface antigen; in three patients antibodies were detected only in CSF. Immunoprecipitation and mass spectrometry showed that the antibodies recognise the B1 subunit of the GABAB receptor, an inhibitory receptor that has been associated with seizures and memory dysfunction when disrupted. Confocal microscopy showed colocalisation of the antibody with GABAB receptors. Seven of 15 patients had tumours, five of which were small-cell lung cancer, and seven patients had non-neuronal autoantibodies. Although nine of ten patients who received immunotherapy and cancer treatment (when a tumour was found) showed neurological improvement, none of the four patients who were not similarly treated improved (p=0.005). Low levels of GABAB1 receptor antibodies were identified in two of 104 controls (p<0.0001). GABAB receptor autoimmune encephalitis is a potentially treatable disorder characterised by seizures and, in some patients, associated with small-cell lung cancer and with other autoantibodies. National Institutes of Health.