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

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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.

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