Elevated EPSTI1 Promote B Cells Hyperactivation through NF-Kb Signaling in Patients with Sjögren ’s Syndrome

Jin-Lei Sun¹, Zhi-Lei Chen², Chao-Feng Lian³, Ti-Hong Shao², Hao-Ze Zhang², Hua Chen³ and Feng-Chun Zhang², ¹Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Beijing, China, ²Peking Union Medical College Hospital, Beijing, China, ³Rheumatology, Peking Union Medical College Hospital, Beijing, China

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: autoimmune diseases and toll-like receptors, B cells, NFB, Sjogren's syndrome

Session Information

Date: Sunday, October 21, 2018

Title: B Cell Biology and Targets in Autoimmune and Inflammatory Disease Poster

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

Sjogren’s syndrome (SS) is a common systemic autoimmune disease characterized with aberrant B cells activation. B cells play a key role in the pathogenesis of SS, however, the abnormal B cell activation in SS is partially understood.

Methods:

We performed whole transcriptome sequencing of B cells from 3 SS patients and 3 matched Healthy controls (HC). We then confirmed the differential gene expressions in 40 SS patients and 40 HC by quantitative PCR and Western-blot. We further transfected with siRNA targeting candidate genes into B cells and stimulated B cells with anti-IgM or CpG to measure the proliferation potential and immunoglobulins secretion. We also explored TLR9 signaling to identify the potential molecular mechanism of B cell hyperactivation in SS.

Results:

We identified 51 up-regulated and 22 down-regulated differentially expression genes in B cells from SS patients. We confirmed the RNA and protein level of EPSTI1(Epithelial Stromal Interaction 1) in B cells from 40 SS patients was significantly higher than those from 40 HCs. Comparing with control B cells, EPSTI1-sliencing B cells stimulated with CpG (but not anti-IgM) were proliferated less and produced lower level of IgG. we observed the level of p-p65, but not pJNK and (p38MAPK), were decreased in EPSTI1-sliencing B cells stimulated with CpG. Consistently, we also found the level of p-p65 was significantly higher in B cells from SS patients than those from HC. Finally, the level of IκBa, a key regulator of p65, was significantly up-regulated in EPSTI1-sliencing B cells and B cells from HC.

Conclusion:

Elevated EPSTI1 expression in B cells from SS patients promoted TLR9 signaling activation and contributed to the abnormal B cells activation. Mechanistically, EPSTI1 stimulated the phosphorylation of p65, which was likely through the interaction and degradation of IκBa.

Disclosure: J. L. Sun, None; Z. L. Chen, None; C. F. Lian, None; T. H. Shao, None; H. Z. Zhang, None; H. Chen, None; F. C. Zhang, None.

To cite this abstract in AMA style:

Sun JL, Chen ZL, Lian CF, Shao TH, Zhang HZ, Chen H, Zhang FC. Elevated EPSTI1 Promote B Cells Hyperactivation through NF-Kb Signaling in Patients with Sjögren ’s Syndrome [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/elevated-epsti1-promote-b-cells-hyperactivation-through-nf-kb-signaling-in-patients-with-sjogren-s-syndrome/. Accessed .

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