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High frequencies of circulating Tfh-Th17 cells in myasthenia gravis patients

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Abstract

Recent studies show that the frequencies of circulating follicullar helper T (cTfh) cells are significantly higher in myasthenia gravis (MG) patients compared with healthy controls (HC). And, they are positively correlated with levels of serum anti-acetylcholine receptor antibody (anti-AchR Ab). It is unclear whether cTfh cell subset frequencies are altered and what role they play in MG patients. In order to clarify this, we examined the frequencies of cTfh cell counterparts, their subsets, and circulating plasmablasts in MG patients by flow cytometry. We determined the concentrations of serum anti-AChR Ab by enzyme-linked immunosorbent assay (ELISA). We assayed the function of cTfh cell subsets by flow cytometry and real-time polymerase chain reaction (RT-PCR). We found higher frequencies of cTfh cell counterparts, cTfh-Th17 cells, and plasmablasts in MG patients compared with HC. The frequencies of cTfh cell counterparts and cTfh-Th17 cells were positively correlated with the frequencies of plasmablasts and the concentrations of anti-AChR Ab in MG patients. Functional assays showed that activated cTfh-Th17 cells highly expressed key molecular features of Tfh cells including ICOS, PD-1, and IL-21. Results indicate that, just like cTfh cell counterparts, cTfh-Th17 cells may play a role in the immunopathogenesis and the production of anti-AChR Ab of MG.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (nos. 81301069 and 31270952). The authors would like to thank all the participants of this study and thank Dr. Austin Cape for careful reading and feedback.

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Author notes

  1. Yongxiang Yang, Min Zhang and Yuqin Ye are equally contributed to the present paper

Authors and Affiliations

  1. Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710038, China

    Yongxiang Yang, Min Zhang & Zhuyi Li

  2. Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China

    Yongxiang Yang & Yuqin Ye

  3. Department of Neurosurgery, PLA 422nd Hospital, Zhanjiang, 524005, China

    Yongxiang Yang

  4. Department of Neurosurgery, PLA 163rd Hospital (Second Affiliated Hospital of Hunan Normal University), Changsha, 410000, China

    Yuqin Ye

  5. Department of Neurology, First Affiliated Hospital of Xi’an Medical University, Xi’an, 710077, China

    Shan Ma & Lingling Fan

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  1. Yongxiang Yang
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Correspondence to Zhuyi Li.

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Compliance with ethical standards

Ethics Committee of the Faculty of Tangdu Hospital gave permission for this research. All the experimental methods in this research were carried out in accordance with the approved guidelines. All the experimental protocols in this research were approved by Ethics Committee of the Faculty of Tangdu Hospital. All patients and healthy volunteers had written informed consent, and all peripheral blood samples were used only for research purpose.

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The authors declare that they have no conflict of interest.

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Yang, Y., Zhang, M., Ye, Y. et al. High frequencies of circulating Tfh-Th17 cells in myasthenia gravis patients. Neurol Sci 38, 1599–1608 (2017). https://doi.org/10.1007/s10072-017-3009-3

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  • DOI: https://doi.org/10.1007/s10072-017-3009-3

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