Encephalitis and antibodies to dipeptidyl-peptidase-like protein-6, a subunit of Kv4.2 potassium channels.
Encephalitis and antibodies to dipeptidyl-peptidase-like protein-6, a subunit of Kv4.2 potassium channels.
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脑炎和抗二肽基肽酶样蛋白6的抗体，Kv4.2钾通道的亚基。
DOI：
10.1002/ana.23756
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发表时间：
2013-01
影响因子：
11.2
通讯作者：
Dalmau, Josep
中科院分区：
文献类型：
--
作者：
Boronat, Anna;Gelfand, Jeffrey M.;Gresa-Arribas, Nuria;Jeong, Hyo-Young;Walsh, Michael;Roberts, Kirk;Martinez-Hernandez, Eugenia;Rosenfeld, Myrna R.;Balice-Gordon, Rita;Graus, Francesc;Rudy, Bernardo;Dalmau, Josep
报道一种新的脑炎细胞表面自身抗原，它是Kv4.2钾通道的关键调节亚基。选择了4例病因不明、抗体与脑组织免疫染色相似的脑炎患者进行自身抗原鉴定。技术包括免疫沉淀、质谱仪、Kv4.2和几种二肽基肽酶样蛋白-6(DPPX)质粒构建物的细胞基础实验，以及野生型和DPPX缺失型小鼠的比较脑免疫染色。免疫沉淀研究确定DPPX为目标自身抗原。一项基于细胞的分析证实，所有4名患者，但不是210名对照，都有DPPX抗体。症状包括躁动、神志不清、肌阵挛、震颤和癫痫(1例伴有明显的惊吓反应)。所有患者都有细胞增多症，三名患者有原因不明的严重前驱腹泻。鉴于DPPX“调节”Kv4.2钾通道(参与躯体树突状细胞信号整合和动作电位树突状后向繁殖的衰减)，我们确定了DPPX、DPP10(一种与DPPX同源的蛋白质)和Kv4.2的表位分布。患者的抗体被发现是DPPX的特异性抗体，不与DPP10或Kv4.2反应。不明原因的腹泻导致了DPPX在肌间神经丛的强烈表达，该神经丛与患者的抗体发生强烈反应。神经精神症状的病程延长，并经常与复发有关，同时减少免疫治疗。长期随访3例有明显改善(1例失访)。DPPX抗体与迁延性脑炎有关，其特征是中枢神经系统过度兴奋(激动、肌阵挛、震颤、癫痫发作)、细胞增多和症状出现时频繁腹泻。这种疾病有可能通过免疫疗法来治疗。
To report a novel cell-surface autoantigen of encephalitis that is a critical regulatory subunit of the Kv4.2 potassium channels. Four patients with encephalitis of unclear etiology and antibodies with a similar pattern of neuropil brain immunostaining were selected for autoantigen characterization. Techniques included immunoprecipitation, mass spectrometry, cell-base experiments with Kv4.2 and several dipeptidyl-peptidase-like protein-6 (DPPX) plasmid constructs, and comparative brain immunostaining of wild-type and DPPX-null mice. Immunoprecipitation studies identified DPPX as the target autoantigen. A cell based assay confirmed that all 4 patients, but not 210 controls, had DPPX antibodies. Symptoms included agitation, confusion, myoclonus, tremor, and seizures (one case with prominent startle response). All patients had pleocytosis, and three had severe prodromal diarrhea of unknown etiology. Given that DPPX “tunes up” the Kv4.2 potassium channels (involved in somatodendritic signal integration and attenuation of dendritic backpropagation of action potentials), we determined the epitope distribution in DPPX, DPP10 (a protein homologous to DPPX) and Kv4.2. Patients’ antibodies were found specific for DPPX, without reacting with DPP10 or Kv4.2. The unexplained diarrhea led to demonstrate a robust expression of DPPX in the myenteric plexus, which strongly reacted with patients’ antibodies. The course of neuropsychiatric symptoms was prolonged and often associated with relapses while decreasing immunotherapy. Long-term follow-up showed substantial improvement in 3 patients (1 is lost to follow-up). Antibodies to DPPX associate with a protracted encephalitis characterized by CNS hyperexcitability (agitation, myoclonus, tremor, seizures), pleocytosis, and frequent diarrhea at symptom onset. The disorder is potentially treatable with immunotherapy.
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影响因子：
11.2
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
通讯作者：
Dalmau, Josep
影响因子：
4.8
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Clark BD;Kwon E;Maffie J;Jeong HY;Nadal M;Strop P;Rudy B
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Rudy B
影响因子：
9.9
作者：
Frechette, Eric S.;Zhou, Lei;Dalmau, Josep
通讯作者：
Dalmau, Josep
影响因子：
2.9
作者：
Nadal, Marcela S.;Amarillo, Yimy;Rudy, Bernardo
通讯作者：
Rudy, Bernardo
影响因子：
6.1
作者：
Singh, Baljinder;Ogiwara, Ikuo;Yamakawa, Kazuhiro
通讯作者：
Yamakawa, Kazuhiro