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Human Cerebrospinal Fluid Monoclonal LGI1 Autoantibodies Increase Neuronal Excitability.

人脑脊液单克隆LGI1自身抗体增加神经元兴奋性。

  • 影响因子:7.43
  • DOI:10.1002/ana.25666
  • 作者列表:"Kornau HC","Kreye J","Stumpf A","Fukata Y","Parthier D","Sammons RP","Imbrosci B","Kurpjuweit S","Kowski AB","Fukata M","Prüss H","Schmitz D
  • 发表时间:2020-03-01
Abstract

OBJECTIVE:Leucine-rich glioma-inactivated 1 (LGI1) encephalitis is the second most common antibody-mediated encephalopathy, but insight into the intrathecal B-cell autoimmune response, including clonal relationships, isotype distribution, frequency, and pathogenic effects of single LGI1 antibodies, has remained limited. METHODS:We cloned, expressed, and tested antibodies from 90 antibody-secreting cells (ASCs) and B cells from the cerebrospinal fluid (CSF) of several patients with LGI1 encephalitis. RESULTS:Eighty-four percent of the ASCs and 21% of the memory B cells encoded LGI1-reactive antibodies, whereas reactivities to other brain epitopes were rare. All LGI1 antibodies were of IgG1, IgG2, or IgG4 isotype and had undergone affinity maturation. Seven of the overall 26 LGI1 antibodies efficiently blocked the interaction of LGI1 with its receptor ADAM22 in vitro, and their mean LGI1 signal on mouse brain sections was weak compared to the remaining, non-ADAM22-competing antibodies. Nevertheless, both types of LGI1 antibodies increased the intrinsic cellular excitability and glutamatergic synaptic transmission of hippocampal CA3 neurons in slice cultures. INTERPRETATION:Our data show that the patients' intrathecal B-cell autoimmune response is dominated by LGI1 antibodies and that LGI1 antibodies alone are sufficient to promote neuronal excitability, a basis of seizure generation. Fundamental differences in target specificity and antibody hypermutations compared to the CSF autoantibody repertoire in N-methyl-D-aspartate receptor encephalitis underline the clinical concept that autoimmune encephalitides are very distinct entities. Ann Neurol 2020;87:405-418.

摘要

目的: 富含亮氨酸的胶质瘤灭活1 (LGI1) 脑炎是第二常见的抗体介导的脑病,但对鞘内b细胞自身免疫反应的了解,包括克隆关系、同种型分布、频率和单一LGI1抗体的致病作用,仍然有限。 方法: 我们从90个抗体分泌细胞 (ASCs) 和几个LGI1脑炎患者脑脊液 (CSF) 的b细胞中克隆、表达和测试抗体。 结果: 21% 的asc和的记忆b细胞编码LGI1-reactive种抗体,而对其他脑表位的反应性很少。所有LGI1抗体均为IgG1、IgG2或IgG4同种型,并经历了亲和力成熟。总体26种LGI1抗体中的7种在体外有效阻断LGI1与其受体ADAM22的相互作用,并且与剩余的non-ADAM22-competing种抗体相比,它们在小鼠脑切片上的平均LGI1信号较弱。然而,两种类型的LGI1抗体增加了切片培养物中海马CA3神经元的固有细胞兴奋性和谷氨酸能突触传递。 解读: 我们的数据显示,患者的鞘内b细胞自身免疫反应由LGI1抗体主导,单独的LGI1抗体足以促进神经元兴奋性,这是癫痫发作产生的基础。在N-甲基-D-天冬氨酸受体脑炎中,与CSF自身抗体库相比,靶特异性和抗体高突变的根本差异强调了自身免疫性脑炎是非常不同的实体的临床概念。Ann Neurol 2020;87:405-418。

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影响因子:2.32
发表时间:2020-01-01
来源期刊:The Laryngoscope
DOI:10.1002/lary.27947
作者列表:["Ji T","Chen J","Mou J","Ni X","Guo Y","Zhang J","Wang S","Wang W","Zhang X","Tai J"]

METHODS:OBJECTIVES/HYPOTHESIS:The definition of large-volume pathologic N1 metastases has been changed in the 2017 version 2 of the National Comprehensive Cancer Network guidelines, leading to a controversy over the optimal surgical approach selection for patients with biopsy-proven papillary thyroid carcinoma (PTC). The aim of this study was to investigate the therapeutic efficacy of total thyroidectomy (TT) and thyroid lobectomy (TL) for these patients. STUDY DESIGN:Retrospective population-based database analysis. METHODS:A total of 906 consecutive PTC patients with pathologic N1 metastases (>5 involved nodes with metastases ≤5 mm in the largest dimension) were retrieved from the Surveillance, Epidemiology, and End Results database, and divided into two groups (≤2 mm, >2-5 mm) based on the size of the extent of disease. Overall survival (OS) was then compared between patients treated with TT and TL, followed by Cox proportional hazards regression analysis to explore multiple prognostic factors. RESULTS:OS favored TT compared with TL in patients with more than five involved nodes and metastases >2 to 5 mm in the largest dimension (P < .05). Cox analysis showed that the TL was not an independent factor associated with poorer OS than TT in these patients (P > .05). CONCLUSIONS:TT showed better survival than TL for patients with more than five involved nodes and metastases >2 to 5 mm in the largest dimension. For patients with more than five involved nodes and metastases ≤2 mm in the largest dimension, either TT or TL can be recommended because there was no difference in survival. LEVEL OF EVIDENCE:NA Laryngoscope, 130:269-273, 2020.

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影响因子:2.09
发表时间:2020-01-01
DOI:10.2174/1573399815666190417145440
作者列表:["Goes LG","da Luz Eltchechem C","Wouk J","Malfatti CRM","da Silva LA"]

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甲状腺疾病方向

主要分为内科治疗的甲状腺疾病和外科治疗的甲状腺疾病两大类。内科治疗的甲状腺疾病主要包括甲状腺功能亢进症和甲状腺炎症。外科治疗的甲状腺疾病包括甲状腺肿和甲状腺肿瘤。

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