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Elevated EPSTI1 promote B cell hyperactivation through NF-κB signalling in patients with primary Sjögren’s syndrome
  1. Jin-lei Sun1,2,
  2. Hao-ze Zhang1,2,
  3. Su-ying Liu1,2,
  4. Chao-feng Lian1,2,
  5. Zhi-lei Chen1,2,
  6. Ti-hong Shao1,2,
  7. Shuo Zhang1,2,
  8. Li-ling Zhao1,2,
  9. Cheng-mei He1,2,
  10. Mu Wang3,
  11. Wen Zhang1,2,
  12. Hua Chen1,2,
  13. Feng-chun Zhang1,2
  1. 1 Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
  2. 2 Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
  3. 3 Department of Stomatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
  1. Correspondence to Hua Chen, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China; chenhua{at}; Feng-chun Zhang; zhangfccra{at}


Background Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterised by aberrant B cell hyperactivation, whose mechanism is partially understood.

Methods We performed whole transcriptome sequencing of B cells from three pSS patients and three matched healthy controls (HC). Differentially expression genes (DEGs) were confirmed with B cells from 40 pSS patients and 40 HC by quantitative PCR and western blot. We measured the proliferation potential and immunoglobulins production of siRNA-transfected or plasmid-transfected B cells stimulated with cytosine-phosphate-guanine (CpG) or anti-IgM. We also explored Toll-like receptor 9 (TLR9) signalling to reveal the potential mechanism of B cell hyperactivation in pSS.

Results We identified 77 upregulated and 32 downregulated DEGs in pSS B cells. We confirmed that epithelial stromal interaction (EPST1) expression in pSS B cells was significantly higher than that from HCs. EPSTI1-silencing B cells stimulated with CpG were less proliferated and produced lower level of IgG and IgM comparing with control B cells. EPSTI1-silencing B cells expressed lower level of p-p65 and higher level of IκBα, and B cells with overexpressed EPSTI1 showed higher level of p-p65 and lower level of IκBα. Finally, IκBα degradation inhibitor Dehydrocostus Lactone treatment attenuated p65 phosphorylation promoted by EPSTI1.

Conclusion Elevated EPSTI1 expression in pSS B cells promoted TLR9 signalling activation and contributed to the abnormal B cell activation, which was promoted by facilitating p65 phosphorylation and activation of NF-κB signalling via promoting IκBα degradation. EPSTI1 might be implicated in pSS pathogenesis and was a potential therapeutic target of pSS.

  • sjøgren's syndrome
  • B cells
  • autoimmune diseases

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  • Handling editor Josef S Smolen

  • HC and F-cZ contributed equally.

  • Contributors HC and FZ conceptualised and designed the project and supervised the project; JS, SL and HZ performed all the experiments and JS wrote the manuscript with contributions from all authors; HC revised the manuscript. CL, ZC, TS, SZ, LZ, CH, MW and WZ participated in the sample collection and clinical analysis. All authors read and approved the manuscript.

  • Funding This study was supported by National Key R&D Program of China (2016YFC0903901, 2016YFA0101003), National Natural Science Fund (81571594, 81771764), CAMS Innovation Fund for Medical Sciences (2016-I2M-1-003, 2017-I2M-3-007), PUMC Youth Fund (3332016005), the Fundamental Research Funds for the Central Universities (3332016005) and 2016 PUMCH Science Fund for Junior Faculty (PUMCH-2016-1.7). The funders had no role in the research or assistance with manuscript preparation.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.

  • Patient consent for publication Obtained.

  • Ethics approval Institutional review board of Peking Union Medical College Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available from the corresponding author upon reasonable request.