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ABS0208 (2025)
THE PATHOGENESIS OF TRANSMEMBRANE ACTIVATOR, CALCIUM MODULATOR AND CYCLOPHILIN LIGAND INTERACTOR (TACI) IN PRIMARY SJOGREN’S SYNDROME AND ITS INTRICATE REGULATION OF B CELLS
Keywords: Biomarkers, Adaptive immunity
H. Zhang1, H. Zhang1, Y. Geng1, X. Zhang1, Y. Wang1, Z. Zhang1
1Peking University First Hospital, Department of Rheumatology and Clinical Immunology, Beijing, China

Background: Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease that mainly affects the lacrimal, salivary and other exocrine glands. More and more studies have shown that B cells play a central role in the pathogenesis of pSS.


Objectives: We intended to explore the expression of the transmembrane activator, calcium modulator and cyclophilin ligand interactor (TACI) on the B cell, its role in pSS, and possible signal transduction pathways.


Methods: We recruited 34 treatment-naive pSS patients and 37 matched healthy controls (HC), to analyze B cell subsets and TACI ratios, along with serum BAFF and sTACI levels. For TACI function, B cells were treated with raw station, siRNA-TACI, and sTACI analog, assessing effects on proliferation and differentiation. TACI-associated signaling pathways were explored by confirming biased miRNA expression via RT-qPCR, screening target genes, and manipulating target gene expression.


Results: pSS patients showed altered peripheral blood B cell subsets, with increased CD19 + CD24 hi CD38 hi regulatory B (Breg) cells and decreased CD19 + CD24 + CD38 - memory B cells, alongside down-regulated TACI expression on B cell subsets and elevated BAFF and sTACI levels in serum. Untreated TACI + B cells in pSS showed increased proliferative capacity. TACI downregulation led to more proliferation, and dysfunctional Breg cells. Telitacicept reduced B cell proliferation, increased transmembrane TACI expression on B cells, and lowered IgG levels. Additionally, hsa-miR-30b-5p was down-regulated in pSS, with its inhibition impairing Breg cell differentiation and IL-10 secretion, correlating with TACI levels, while SMAD1-Id2 was identified as its target gene in the TGF-β/Hippo pathway.


Conclusion: B cell impairment, especially in Breg subsets, is linked to low TACI expression, which is associated with reduced hsa-miR-30b-5p, activating the TGF-β/Hippo pathway through SMAD1/Id2, contributing to pSS pathogenesis.


REFERENCES: NIL.


Acknowledgements: NIL.


Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.


DOI: annrheumdis-2025-eular.A390
Keywords: Biomarkers, Adaptive immunity
Citation: , volume 84, supplement 1, year 2025, page 2075
Session: Sjögren’s syndrome (Publication Only)