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Longitudinal omics reveals immune repertoire remodeling in myasthenia gravis patients post-tacrolimus therapy

Genes & Immunity (2026)Cite this article

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Abstract

Myasthenia gravis (MG) is a T/B cell-driven autoimmune disease. The immunomodulatory mechanisms of the common immunosuppressant tacrolimus (TAC) on the immune repertoire are unclear. This study investigated TAC’s immunomodulatory effects via high-throughput sequencing of peripheral blood mononuclear cells from four MG patients pre- and post-four months of TAC monotherapy, revealing dynamic T-cell receptor (TCR) and B-cell receptor (BCR) repertoire remodeling. The immune repertoire of MG patients was characterized by a skewed usage of TRBV gene families compared to healthy controls, indicating an underlying immune dysfunction. Longitudinal analysis post-TAC therapy revealed potential downregulation of IGHV1-69 and IGHV3-43 gene frequencies (p < 0.05, FDR > 0.1), alongside non-significant trends toward shorter CDR3 lengths and reduced clonal diversity in both IGH and TRB (p > 0.05). The BCR repertoire underwent greater dynamic remodeling, while the TCR repertoire remained relatively stable, as evidenced by the persistence of dominant clones and overlapping TRB clones. BCR diversity and V or J gene usage in TCR and BCR showed potential associations with clinical severity. These data reveal skewed antigen recognition profiles in MG pathogenesis, with TAC orchestrating multimodal immunomodulation through peripheral immune repertoire reshaping.

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Fig. 1: V gene family usage profiles in MG patients versus HC.
Fig. 2: Changes in IGHV gene usage in MG during a 4-month follow-up.
Fig. 3: CDR3 sequence lengths in HC and MG patients before and after TAC therapy.
Fig. 4: BCR and TCR clonal diversity in HC and MG patients before and after TAC therapy.
Fig. 5: Shared amino acid among MG patients and before and after TAC therapy.
Fig. 6: Longitudinal analysis of dominant clones in MG patients before and after TAC therapy.
Fig. 7: Correlation analysis between CDR3 diversity, V/J genes and disease activity in patients with MG.

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Data availability

The data that support the findings of this study are available on request from the corresponding author.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (Grand No. 82371413 to Huan Yang).

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Authors and Affiliations

  1. Department of Neurology, Xiangya Hospital, Central South University, Changsha, China

    Ting He, Liu Wang, Kangzhi Chen, Qian Zhou, Liqun Xu, Zhaohui Luo & Huan Yang

  2. Research Center for Neuroimmune and Neuromuscular Disorders, Xiangya Hospital, Central South University, Changsha, PR China

    Ting He, Liu Wang, Kangzhi Chen, Qian Zhou, Liqun Xu, Zhaohui Luo & Huan Yang

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Contributions

Huan Yang: conception, study design, funding acquisition, writing-review and editing; Ting He: writing-original draft, formal analysis, and visualization; Liu Wang: formal analysis, software, and visualization; Kangzhi Chen: data collection and software; Qian Zhou: data curation and investigation; Liqun Xu and Zhaohui Luo: writing-review and editing and supervision. All authors contributed to the article and approved the final manuscript.

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Correspondence to Huan Yang.

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He, T., Wang, L., Chen, K. et al. Longitudinal omics reveals immune repertoire remodeling in myasthenia gravis patients post-tacrolimus therapy. Genes Immun (2026). https://doi.org/10.1038/s41435-026-00395-1

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