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. 2025 Mar;30(1):e70006.
doi: 10.1111/jns.70006.

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

G G A van Lieverloo  1   2 , D C Anang  1   3 , M E Adrichem  2   4 , B A Coert  5 , A E Aronica  6 , L Wieske  2   7 , I N van Schaik  2   8 , N de Vries  1 , F Eftimov  2
Affiliations

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

G G A van Lieverloo et al. J Peripher Nerv Syst. 2025 Mar.

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.

Keywords: CIDP; T‐cell receptor repertoire; clonality; nerve; next‐generation sequencing.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Scatter plot of the TCRβ repertoire in nerve tissues and peripheral blood of treatment‐naive CIDP patients. Each dot represents a unique TCRβ clone expressed as a percentage of the total TCRβ repertoire. TCRβ clones in blood with a frequency ≥ 0.5% of the total TCRβ repertoire are considered highly expanded clones (HECs). There are no pre‐defined cut‐off values for TCRβ clones in nerve tissue.
FIGURE 2
FIGURE 2
CDR3 clonal overlap plots between peripheral blood (X‐axis) and nerve tissue (Y‐axis) for (A) Patient A, (B) Patient B and (C) Patient C. Each dot represents a unique TCRβ clone, and its frequency in the analyzed repertoires is depicted on the x (peripheral blood) and y (nerve tissue) axes. The dotted lines indicate the 0.5% cut‐off for dominant TCRβ clones in blood.
See this image and copyright information in PMC

References

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