Intrathecal B-cell activation in LGI1 antibody encephalitis
Intrathecal B-cell activation in LGI1 antibody encephalitis
复制标题
DOI：
10.1212/nxi.0000000000000669
复制
发表时间：
2020-03-01
影响因子：
8.8
通讯作者：
von Budingen, H. -Christian
中科院分区：
文献类型：
--
作者：
Lehmann-Horn, Klaus;Irani, Sarosh R.;von Budingen, H. -Christian
目的研究富含亮氨酸胶质瘤灭活1（LGI1）抗体脑炎患者鞘内B细胞活性。在LGI1抗体患者中，CSF淋巴细胞增多或寡克隆带和血清主要LGI1抗体的缺乏表明外周启动的免疫应答。然而，尚不清楚CNS内的B细胞是否有助于LGI 1抗体脑炎的持续发病机制。方法收集6例LGI 1抗体脑炎患者和2例其他神经系统疾病患者的脑脊液和外周血单个核细胞。对来自CSF B细胞和分选的PB B细胞亚群的免疫球蛋白重链转录物进行深度B细胞免疫库测序。此外，还测定了CSF和PB中的LGI1抗体水平。结果血清LGI1抗体滴度平均为脑脊液LGI1抗体滴度的127倍。然而，深层B细胞库分析显示了有限的CSF库，其中克隆相关的B细胞的频繁广泛簇连接到成熟的PB B细胞。这些簇显示出CSF B细胞的强烈突变活性，为LGI 1抗体脑炎患者中独立的基于CNS的抗原驱动的应答提供了强有力的证据，但在对照组中没有。结论我们的研究结果表明，鞘内免疫球蛋白库扩张是LGI1抗体脑炎的一个特点，并建议需要CNS渗透治疗。
Objective To study intrathecal B-cell activity in leucine-rich, glioma-inactivated 1 (LGI1) antibody encephalitis. In patients with LGI1 antibodies, the lack of CSF lymphocytosis or oligoclonal bands and serum-predominant LGI1 antibodies suggests a peripherally initiated immune response. However, it is unknown whether B cells within the CNS contribute to the ongoing pathogenesis of LGI1 antibody encephalitis. Methods Paired CSF and peripheral blood (PB) mononuclear cells were collected from 6 patients with LGI1 antibody encephalitis and 2 patients with other neurologic diseases. Deep B-cell immune repertoire sequencing was performed on immunoglobulin heavy chain transcripts from CSF B cells and sorted PB B-cell subsets. In addition, LGI1 antibody levels were determined in CSF and PB. Results Serum LGI1 antibody titers were on average 127-fold higher than CSF LGI1 antibody titers. Yet, deep B-cell repertoire analysis demonstrated a restricted CSF repertoire with frequent extensive clusters of clonally related B cells connected to mature PB B cells. These clusters showed intensive mutational activity of CSF B cells, providing strong evidence for an independent CNS-based antigen-driven response in patients with LGI1 antibody encephalitis but not in controls. Conclusions Our results demonstrate that intrathecal immunoglobulin repertoire expansion is a feature of LGI1 antibody encephalitis and suggests a need for CNS-penetrant therapies.