Unique Nerve Tissue-Restricted T-Cell Clones in Chronic Inflammatory Demyelinating Polyneuropathy

IF 3.9 3区 医学 Q1 CLINICAL NEUROLOGY
G. G. A. van Lieverloo, D. C. Anang, M. E. Adrichem, B. A. Coert, A. E. Aronica, L. Wieske, I. N. van Schaik, N. de Vries, F. Eftimov
{"title":"Unique Nerve Tissue-Restricted T-Cell Clones in Chronic Inflammatory Demyelinating Polyneuropathy","authors":"G. G. A. van Lieverloo,&nbsp;D. C. Anang,&nbsp;M. E. Adrichem,&nbsp;B. A. Coert,&nbsp;A. E. Aronica,&nbsp;L. Wieske,&nbsp;I. N. van Schaik,&nbsp;N. de Vries,&nbsp;F. Eftimov","doi":"10.1111/jns.70006","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background and Aims</h3>\n \n <p>Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated disorder characterized by peripheral nerve damage. Although T lymphocytes (T-cells) are implicated in the pathogenesis of CIDP, we previously observed that the frequency of highly expanded T-cell clones (HECs) in peripheral blood of CIDP patients was not different from healthy controls. To investigate if local T-cells might be pathogenic, we employed next-generation sequencing to compare the TCRβ repertoire between peripheral blood and nerve tissue of CIDP patients.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Adaptive immune receptor repertoire sequencing (AIRR-Seq) of the TCRβ chain was conducted on peripheral blood and nerve tissue obtained from three newly diagnosed CIDP patients.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>All patients showed high numbers of highly expanded TCRβ clones in nerve tissue that were not detected or detected only in very low frequencies in blood, whereas in blood other HECs were found. Clustering analysis based on CDR3-similarity showed that these nerve tissue-restricted TCRβ clones were distinct from blood clones, as evidenced by the absence of prominent clusters.</p>\n </section>\n \n <section>\n \n <h3> Interpretation</h3>\n \n <p>Unique nerve tissue-restricted TCRβ clones may indicate a highly localized immune response with localized expansion and/or retention of T-cells that could contribute to the pathomechanism of CIDP.</p>\n \n <p>Further characterization of the phenotype, antigen target and functionality of these T-cells is essential to determine their pathogenic role.</p>\n </section>\n </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 1","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.70006","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the Peripheral Nervous System","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/jns.70006","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background and Aims

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated disorder characterized by peripheral nerve damage. Although T lymphocytes (T-cells) are implicated in the pathogenesis of CIDP, we previously observed that the frequency of highly expanded T-cell clones (HECs) in peripheral blood of CIDP patients was not different from healthy controls. To investigate if local T-cells might be pathogenic, we employed next-generation sequencing to compare the TCRβ repertoire between peripheral blood and nerve tissue of CIDP patients.

Methods

Adaptive immune receptor repertoire sequencing (AIRR-Seq) of the TCRβ chain was conducted on peripheral blood and nerve tissue obtained from three newly diagnosed CIDP patients.

Results

All patients showed high numbers of highly expanded TCRβ clones in nerve tissue that were not detected or detected only in very low frequencies in blood, whereas in blood other HECs were found. Clustering analysis based on CDR3-similarity showed that these nerve tissue-restricted TCRβ clones were distinct from blood clones, as evidenced by the absence of prominent clusters.

Interpretation

Unique nerve tissue-restricted TCRβ clones may indicate a highly localized immune response with localized expansion and/or retention of T-cells that could contribute to the pathomechanism of CIDP.

Further characterization of the phenotype, antigen target and functionality of these T-cells is essential to determine their pathogenic role.

Abstract Image

慢性炎性脱髓鞘性多神经病变中独特的神经组织限制性t细胞克隆
背景与目的慢性炎症性脱髓鞘性多神经病变(CIDP)是一种以周围神经损伤为特征的免疫介导性疾病。尽管T淋巴细胞(T细胞)与CIDP的发病机制有关,但我们之前观察到CIDP患者外周血中高度扩增的T细胞克隆(HECs)的频率与健康对照组没有差异。为了研究局部t细胞是否可能致病,我们采用新一代测序方法比较了CIDP患者外周血和神经组织之间的TCRβ库。方法对3例新诊断的CIDP患者外周血和神经组织进行TCRβ链适应性免疫受体库测序(AIRR-Seq)。结果所有患者均在神经组织中发现大量高扩增的TCRβ克隆,而在血液中未检测到或仅在极低频率中检测到,而在血液中发现了其他hec。基于cdr3相似性的聚类分析表明,这些神经组织限制性TCRβ克隆与血液克隆不同,没有明显的聚类。独特的神经组织限制性TCRβ克隆可能表明高度局部化的免疫反应,局部扩张和/或保留t细胞,可能有助于CIDP的病理机制。进一步表征这些t细胞的表型、抗原靶点和功能对于确定其致病作用至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
6.10
自引率
7.90%
发文量
45
审稿时长
>12 weeks
期刊介绍: The Journal of the Peripheral Nervous System is the official journal of the Peripheral Nerve Society. Founded in 1996, it is the scientific journal of choice for clinicians, clinical scientists and basic neuroscientists interested in all aspects of biology and clinical research of peripheral nervous system disorders. The Journal of the Peripheral Nervous System is a peer-reviewed journal that publishes high quality articles on cell and molecular biology, genomics, neuropathic pain, clinical research, trials, and unique case reports on inherited and acquired peripheral neuropathies. Original articles are organized according to the topic in one of four specific areas: Mechanisms of Disease, Genetics, Clinical Research, and Clinical Trials. The journal also publishes regular review papers on hot topics and Special Issues on basic, clinical, or assembled research in the field of peripheral nervous system disorders. Authors interested in contributing a review-type article or a Special Issue should contact the Editorial Office to discuss the scope of the proposed article with the Editor-in-Chief.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信