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 (