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CD19+ Tim-1+ B cells are decreased and negatively correlated with disease severity in Myasthenia Gravis patients

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Abstract

T cell immunoglobulin mucin domain-1(Tim-1) was recently identified to be critical and essential for optimal regulatory B cells function in maintaining immune tolerance. We aimed to measure the expression levels of Tim-1 on B cells from patients with Myasthenia Gravis (MG) and to investigate whether the expression of Tim-1 is associated with pathogenesis of MG. A total of 34 patients with MG (18 generalized MG (GMG) and 16 ocular MG (OMG) and 24 healthy donors were recruited in this study. The quantitative myasthenia gravis score (QMGS) was used to evaluate the clinical severity. Real-time PCR and flow cytometry were used to measure the levels of Tim-1 expressed on peripheral B cells. Peripheral CD138+ plasma cells were assayed by flow cytometry. Serum Th17-related cytokines (IL-6, IL-1β and IL-17) and anti-AChR antibody (Ab) titers were tested by enzyme-linked immunosorbent assay (ELISA). Our data demonstrated that the mRNA and protein expression levels of B cell Tim-1 in both the GMG and OMG groups were significantly lower than those in healthy controls, with lower expression in GMG than in OMG. Tim-1 expression on B cells from OMG/GMG was negatively correlated with clinical severity, plasma cells frequency, serum Th17-related cytokines and anti-AChR Ab levels. Our results indicated that aberrant expression of Tim-1 exists on B cells and may contribute to the Th17 polarization and antibody-secreting plasma cells differentiation in MG patients.

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Acknowledgments

We would like to thank all patients and normal control persons for their collaboration. This work was supported by National Nature Science Foundation of China (81571579, 81072465), Natural Science Fund of the Educational Committee of Jiangsu Province (10KJD320003), Special foundation of president of the Xuzhou Medical College (2010KJZ01), Key medical talents fund of Jiangsu Province (H201130), Jiangsu Province ordinary university postgraduate research innovation fund (CXLX11_0734), Innovation and entrepreneurship training program for college students in Jiangsu Province (201610313038Y).

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    1. Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China

      Yong Zhang, Xiuying Zhang, Yan Xia, Xiao Jia, Hao Li, Yanyan Zhang, Zhen Shao, Ning Xin, Jing Chen, ShuangShuang Zheng, Chenghua Xiao, Deqin Geng, Yonghai Liu, Guiyun Cui, Ruiguo Dong, Xiaoyu Huang & Tingyan Yu

    2. Department of Neurology, Shenzhen Guangming New District Central Hospital, Shenzhen, China

      Xiuying Zhang

    3. Department of Neurology, The Third People’s Hospital of Xuzhou, Xuzhou, Jiangsu, China

      Yanyan Zhang

    4. Department of Emergency Medicine, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu, China

      Mingfeng Guo

    5. Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China

      YuZhong Wang

    6. Department of Pathogenic Biology and Lab of Infection and Immunology, Xuzhou Medical College, Xuzhou, Jiangsu, China

      Linlin Fu

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    1. Yong Zhang
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    Correspondence to Yong Zhang or Chenghua Xiao.

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    Yong Zhang, Xiuying Zhang and Yan Xia have contributed equally to this work.

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    Zhang, Y., Zhang, X., Xia, Y. et al. CD19+ Tim-1+ B cells are decreased and negatively correlated with disease severity in Myasthenia Gravis patients. Immunol Res 64, 1216–1224 (2016). https://doi.org/10.1007/s12026-016-8872-0

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