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Increased expression of Bruton’s tyrosine kinase in peripheral blood is associated with lupus nephritis

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Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease manifested by multiorgan impairment. It is reported that B cells participate in the onset of SLE. Bruton’s tyrosine kinase (Btk), as a downstream signaling molecule of B cell antigen receptor (BCR) signaling pathway, is involved in the development, activation, and survival of B cells. The aim of our study was to explore the specific role of Btk in lupus nephritis (LN). We determined the percentages of Btk+ B cells in peripheral blood mononuclear cells (PBMCs) from SLE patients by flow cytometry and analyzed the correlation between the percentage of Btk+ B cells and lupus-related clinical indexes. Immunohistochemistry was used to detect the Btk expression in kidney from LN patients and tumor surrounding tissues. Compared with controls, the frequency of Btk+ B cells in SLE patients was upregulated (p < 0.01), and it was significantly correlated with the SLE Disease Activity Index (SLEDAI) (p < 0.01), levels of plasma anti-dsDNA antibody (p < 0.05), the amount of 24-h urine protein (p < 0.05), and levels of plasma C3 (p < 0.05). The frequency of Btk+ B cells in the patients with LN was significantly higher than those without LN (p < 0.05). Although the Btk expression in glomerulus of LN patients was significantly increased compared with controls (p < 0.001), but it had no correlation with the renal pathology activity index, SLEDAI, or 24-h urine protein. In conclusion, the increased expression of Btk in peripheral blood was correlated with LN, indicating that it may be a therapeutic target for SLE.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81273304, 81401349, 81601414), the fundamental Research Funds for the Central Universities of China (No. 021414340284), and Jiangsu Province Major Research and Development Program (No. BE2015602).

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Authors and Affiliations

  1. Department of Rheumatology & Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, 210008, China

    Wei Kong, Wei Deng, Yue Sun, Saisai Huang, Zhuoya Zhang, Bingyu Shi, Weiwei Chen, Xiaojun Tang, Genhong Yao, Xuebing Feng & Lingyun Sun

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  1. Wei Kong
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  2. Wei Deng
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  3. Yue Sun
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  4. Saisai Huang
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  5. Zhuoya Zhang
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  6. Bingyu Shi
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  7. Weiwei Chen
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  8. Xiaojun Tang
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  9. Genhong Yao
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  10. Xuebing Feng
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  11. Lingyun Sun
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Correspondence to Lingyun Sun.

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All the research with human subjects was in compliance with the Helsinki Declaration. The study was approved by the Ethics Committee of the Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University.

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Kong, W., Deng, W., Sun, Y. et al. Increased expression of Bruton’s tyrosine kinase in peripheral blood is associated with lupus nephritis. Clin Rheumatol 37, 43–49 (2018). https://doi.org/10.1007/s10067-017-3717-3

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  • DOI: https://doi.org/10.1007/s10067-017-3717-3

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