Clonal hematopoiesis in LGI1-antibody encephalitis

IF 4.4 2区医学 Q1 CLINICAL NEUROLOGY Annals of Clinical and Translational Neurology Pub Date : 2024-08-28 DOI:10.1002/acn3.52192

Soo Jean Shin, Yoonhyuk Jang, Soo Hyun Ahn, Su Yee Mon, Ji Hye You, Hong Yul An, Choong Hyun Sun, Youngil Koh, Kon Chu, Sang Kun Lee, Soon-Tae Lee

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Abstract

Objective

Leucine-rich glioma-inactivated 1 (LGI1)-antibody encephalitis (LGI1e), the major form of autoimmune encephalitis (AE) presented with memory loss and faciobrachial dystonic seizure, commonly develops in aged population. Hematologic aging is often accompanied by clonal hematopoiesis (CH), a phenomenon in which specific mutations accumulate, potentially leading to autoimmune disorders or malignancies. Our research aimed to investigate the connection between clonal hematopoiesis of indeterminate potential (CHIP) and LGI1e.

Methods

Peripheral blood samples from consecutive LGI1e patients were collected and analyzed for 24 clonal CHIP using targeted gene sequencing. The results were compared to a control dataset from an ethnically matched health care cohort. Patient characteristics were analyzed based on their CHIP status.

Results

A total of 52 LGI1e patients were enrolled for this study. Among them, three patients (5.8%) exhibited functional mutations in the ASXL1 gene, one of the CHIP-associated genes analyzed by targeted sequencing. This frequency was significantly higher compared to that of the control cohort (1%, p = 0.015). Nevertheless, the patients showed no difference in the clinical characteristics, laboratory results, and immunotherapy outcomes.

Interpretation

LGI1e showed high frequency of ASXL1 functional mutation in the CHIP analysis, which may contribute to the underlying pathogenesis. Further research is needed to determine its direct role in the development of autoimmunity and disease progression.

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LGI1-抗体脑炎中的克隆性造血。

目的：富亮氨酸胶质瘤灭活1（LGI1）抗体脑炎（LGI1e）是自身免疫性脑炎（AE）的一种主要形式，表现为记忆力减退和面肌强直发作，常见于老年人群。血液学衰老通常伴随着克隆性造血（CH），这是一种特定突变积累的现象，可能导致自身免疫性疾病或恶性肿瘤。我们的研究旨在探讨不确定潜能克隆性造血（CHIP）与 LGI1e 之间的联系：方法：收集连续 LGI1e 患者的外周血样本，并通过靶向基因测序分析 24 个克隆 CHIP。结果与来自种族匹配的医疗保健队列的对照数据集进行了比较。根据CHIP状态对患者特征进行了分析：本研究共招募了 52 名 LGI1e 患者。其中，3 名患者（5.8%）的 ASXL1 基因出现功能性突变，而 ASXL1 基因是通过靶向测序分析的 CHIP 相关基因之一。这一频率明显高于对照组（1%，P = 0.015）。尽管如此，患者的临床特征、实验室结果和免疫治疗结果均无差异：LGI1e在CHIP分析中显示出高频率的ASXL1功能突变，这可能与潜在的发病机制有关。解读：CHIP分析显示，LGI1e的ASXL1功能突变频率较高，这可能是其潜在的发病机制之一，需要进一步研究以确定其在自身免疫和疾病进展中的直接作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Clinical and Translational Neurology Medicine-Neurology (clinical)

CiteScore

9.10

自引率

1.90%

发文量

218

审稿时长

8 weeks

期刊介绍： Annals of Clinical and Translational Neurology is a peer-reviewed journal for rapid dissemination of high-quality research related to all areas of neurology. The journal publishes original research and scholarly reviews focused on the mechanisms and treatments of diseases of the nervous system; high-impact topics in neurologic education; and other topics of interest to the clinical neuroscience community.