AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location.
AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location.
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DOI：
10.1002/ana.21589
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发表时间：
2009-04
影响因子：
11.2
通讯作者：
Dalmau, Josep
中科院分区：
文献类型：
--
作者：
Lai, Meizan;Hughes, Ethan G.;Peng, Xiaoyu;Zhou, Lei;Gleichman, Amy J.;Shu, Huidy;Mata, Sabrina;Kremens, Daniel;Vitaliani, Roberta;Geschwind, Michael D.;Bataller, Luis;Kalb, Robert G.;Davis, Rebecca;Graus, Francesc;Lynch, David R.;Balice-Gordon, Rita;Dalmau, Josep
边缘脑炎（LE）经常与细胞表面抗原的抗体有关。这些抗原的表征是重要的，因为它有助于诊断那些对治疗有反应的疾病。我们报告了一种新的LE抗原和患者的抗体对神经元培养的影响。LE 10例临床分析免疫沉淀和质谱用于鉴定抗原。将表达抗原的HEK 293细胞用于免疫细胞化学和ELISA。用共聚焦显微镜测定患者抗体对活的大鼠海马神经元培养物的影响。中位年龄为60岁（38-87岁）; 9例为女性。其中7人患有肺、乳腺或胸腺肿瘤。9例患者对免疫治疗或肿瘤治疗有反应，但神经系统复发（无肿瘤复发）频繁，并影响长期结局。1例未经治疗的患者死于LE。所有患者都有针对神经元细胞表面抗原的抗体，通过免疫沉淀法发现这些抗原是AMPA受体（AMPAR）的GluR 1和GluR 2亚基。表达GluR 1/2的HEK 293细胞与所有患者的血清或CSF发生反应，为该疾病提供了诊断测试。应用抗体培养的神经元显着减少了数量的GluR 2-含有AMPAR集群在突触的整体AMPAR集群密度的一个较小的减少，这些影响被逆转后，抗体去除。GluR 1/2抗体与LE相关，LE通常是副肿瘤性的，治疗反应性的，并且有复发的趋势。我们的研究结果支持抗体介导的发病机制，其中患者的抗体改变了AMPAR的突触定位和数量。
Limbic encephalitis (LE) frequently associates with antibodies to cell surface antigens. Characterization of these antigens is important because it facilitates the diagnosis of those disorders that are treatment-responsive. We report a novel antigen of LE and the effect of patients' antibodies on neuronal cultures. Clinical analysis of 10 patients with LE. Immunoprecipitation and mass spectrometry were used to identify the antigens. HEK293 cells expressing the antigens were used in immunocytochemistry and ELISA. The effect of patients' antibodies on cultures of live rat hippocampal neurons was determined with confocal microscopy. Median age was 60 years (38-87); 9 were women. Seven had tumors of the lung, breast or thymus. Nine patients responded to immunotherapy or oncological therapy but neurologic relapses, without tumor recurrence, were frequent and influenced the long-term outcome. One untreated patient died of LE. All patients had antibodies against neuronal cell surface antigens that by immunoprecipitation were found to be the GluR1 and GluR2 subunits of the AMPA receptor (AMPAR). HEK293 cells expressing GluR1/2 reacted with all patients' sera or CSF, providing a diagnostic test for the disorder. Application of antibodies to cultures of neurons significantly decreased the number of GluR2-containing AMPAR clusters at synapses with a smaller decrease in overall AMPAR cluster density; these effects were reversed after antibody removal. Antibodies to GluR1/2 associate with LE that is often paraneoplastic, treatment-responsive, and has a tendency to relapse. Our findings support an antibody-mediated pathogenesis in which patients' antibodies alter the synaptic localization and number of AMPAR.
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影响因子：
9.9
作者：
Graus F;Saiz A;Lai M;Bruna J;López F;Sabater L;Blanco Y;Rey MJ;Ribalta T;Dalmau J
通讯作者：
Dalmau J
影响因子：
14.5
作者：
CORSELLIS, JA;GOLDBERG, GJ;NORTON, AR
通讯作者：
NORTON, AR
影响因子：
48
作者：
Dalmau, Josep;Gleichman, Amy J.;Hughes, Ethen G.;Rossi, Jeffrey E.;Peng, Xiaoyu;Lai, Meizan;Dessain, Scott K.;Rosenfeld, Mynna R.;Balice-Gordon, Rita;Lynch, David R.
通讯作者：
Lynch, David R.
影响因子：
11
作者：
Bataller, L.;Kleopa, K. A.;Dalmau, J.
通讯作者：
Dalmau, J.
DOI：
10.1111/j.1440-1681.2007.04722.x
发表时间：
2007-10-01
影响因子：
2.9
作者：
Genoux, David;Montgomery, Johanna M.
通讯作者：
Montgomery, Johanna M.