Monoclonal antibodies from a patient with anti-NMDA receptor encephalitis.
Monoclonal antibodies from a patient with anti-NMDA receptor encephalitis.
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DOI：
10.1002/acn3.592
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发表时间：
2018-08
影响因子：
5.3
通讯作者：
Dessain SK
中科院分区：
文献类型：
--
作者：
Sharma R;Al-Saleem FH;Panzer J;Lee J;Puligedda RD;Felicori LF;Kattala CD;Rattelle AJ;Ippolito G;Cox RH;Lynch DR;Dessain SK
抗NMDA受体脑炎(ANRE)是一种潜在的致命性脑炎，由N-甲基-D-天冬氨酸受体(NMDAR)自身抗体引起。我们试图克隆和鉴定一例ANRE患者的单抗。我们用杂交瘤的方法从一位无畸胎瘤的女性ANRE患者身上克隆了两株免疫球蛋白单抗，并测定了它们与NMDAR转基因细胞系、原代培养的大鼠神经元和小鼠海马神经元的结合活性。我们还评估了它们对小鼠自主活动和体内与NMDAR结合的影响。单抗在结构上是不同的，来自不同的B细胞谱系。它们识别GluN1氨基末端结构域(ATD)上的不同表位，但都需要对翻译后修饰很重要的氨基酸。这两种单抗都与培养的大鼠海马神经元上的GluN1亚群结合。5F5单抗与小鼠脑海马区组织结合，培养的大鼠神经元上识别的GluN1基本上是突触外的。抗体与原代海马神经元结合可诱导受体内化。NMDAR抑制剂MK-801抑制单抗内化但不阻止单抗结合；AP5既抑制单抗结合又抑制单抗内化。与低剂量的NMDAR抑制剂MK-801相似，在血脑屏障通透性增强后，小鼠暴露于mAbs可以增加自主车轮跑的活动。这些单抗概括了以往对ANRE患者脑脊液的研究，并在体外和体内对NMDAR发挥作用，与对NMDAR活性的调节一致。
Anti‐NMDA receptor encephalitis (ANRE) is a potentially lethal encephalitis attributed to autoantibodies against the N‐methyl‐D‐aspartate receptor (NMDAR). We sought to clone and characterize monoclonal antibodies (mAbs) from an ANRE patient. We used a hybridoma method to clone two IgG mAbs from a female patient with ANRE without teratoma, and characterized their binding activities on NMDAR‐transfected cell lines, cultured primary rat neurons, and mouse hippocampus. We also assessed their effects on voluntary locomotor activity in mice and binding to NMDAR in vivo. The mAbs are structurally distinct and arose from distinct B‐cell lineages. They recognize different epitopes on the GluN1 amino terminal domain (ATD), yet both require amino acids important for post‐translational modification. Both mAbs bind subsets of GluN1 on cultured rat hippocampal neurons. The 5F5 mAb binds mouse brain hippocampal tissues, and the GluN1 recognized on cultured rat neurons was substantially extra‐synaptic. Antibody binding to primary hippocampal neurons induced receptor internalization. The NMDAR inhibitor MK‐801 inhibited internalization without preventing mAb binding; AP5 inhibited both mAb binding and internalization. Exposure of mice to the mAbs following permeabilization of the blood brain barrier increased voluntary wheel running activity, similar to low doses of the NMDAR inhibitor, MK‐801. These mAbs recapitulate features demonstrated in previous studies of ANRE patient CSF, and exert effects on NMDAR in vitro and in vivo consistent with modulation of NMDAR activity.
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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：
2.5
作者：
Jangula A;Murphy EJ
通讯作者：
Murphy EJ
DOI：
10.1016/j.jpeds.2012.10.011
发表时间：
2013-04
期刊：
The Journal of pediatrics
影响因子：
--
作者：
Armangue T;Titulaer MJ;Málaga I;Bataller L;Gabilondo I;Graus F;Dalmau J;Spanish Anti-N-methyl-D-Aspartate Receptor (NMDAR) Encephalitis Work Group
通讯作者：
Spanish Anti-N-methyl-D-Aspartate Receptor (NMDAR) Encephalitis Work Group
影响因子：
5.4
作者：
Lim, Theam Soon;Mollova, Svetlana;Konthur, Zoltan
通讯作者：
Konthur, Zoltan
影响因子：
14.5
作者：
Kreye, Jakob;Wenke, Nina K.;Pruss, Harald
通讯作者：
Pruss, Harald