van Lieverloo G G A, Anang D C, Adrichem M E, Coert B A, Aronica A E, Wieske L, van Schaik I N, de Vries N, Eftimov F
Amsterdam Rheumatology and Immunology Center Amsterdam, Department of Clinical Immunology and Rheumatology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
J Peripher Nerv Syst. 2025 Mar;30(1):e70006. doi: 10.1111/jns.70006.
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.
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.
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.
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.
慢性炎性脱髓鞘性多发性神经病（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（HEC）频率与健康对照并无差异。为了研究局部T细胞是否具有致病性，我们采用新一代测序技术比较CIDP患者外周血和神经组织之间的TCRβ库。
对3例新诊断的CIDP患者的外周血和神经组织进行TCRβ链的适应性免疫受体库测序（AIRR-Seq）。
所有患者的神经组织中均显示出大量高度扩增的TCRβ克隆，这些克隆在血液中未被检测到或仅以极低频率被检测到，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，这一点通过缺乏显著聚类得以证明。
独特的神经组织限制性TCRβ克隆可能表明存在高度局部化的免疫反应，伴有T细胞的局部扩增和/或滞留，这可能有助于CIDP的发病机制。进一步表征这些T细胞的表型、抗原靶点和功能对于确定它们的致病作用至关重要。
