Background: Primary Sjögren syndrome (pSjS) is a common autoimmune disease with cardinal feature of exocrinopathy, which characterized dryness of mouth and eyes and progressive loss of salivary and lacrimal gland function [1]. Regulatory T (Treg) cells are essential for maintaining self-tolerance and preventing autoimmune diseases. Dysfunction of Treg cells contributed to pSjS development [2]. However, the role of Treg dysregulation in the pathogenesis of pSjS was not fully elucidated due to the complexity of this disorder.

Objectives: The aim of the study was to investigate the dysregulation of Treg cells in patients with pSjS.

Methods: We enrolled patients with pSjS who visited Taipei Veterans General Hospital, Taipei, Taiwan. Treg cell-associated molecules, including programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), lymphocyte activation gene 3 (LAG-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), and T-cell immunoglobulin and mucin domain-containing 3 (Tim-3), were determined by flow cytometry. Cytokine expression was also analyzed to know whether Tregs retain their suppressive ability in pSjS.

Results: Twenty patients with pSjS and 20 health controls (HCs) were enrolled. The mean age at diagnosis of pSjS was 51.0 years and disease duration were 5.75 years. This study did not reveal notable differences in the frequency of lymphocytes, CD4+ Tcells, and CD4+ FoxP3+ Treg cells between two groups (p = 0.583, 0.165, and 0.102, respectively). Interestingly, the mean fluorescent intensity (MFI) of FoxP3 in CD4+ FoxP3+ Treg cells was significantly higher in pSjS patients compared to HCs (1714 ± 698 vs. 1180 ± 404, p = 0.15). It is worth noting that the percentage of PD-1+ cells of CD4+ FoxP3+ T cells was significantly higher in the peripheral blood of pSjS compared to HCs (4.9 ± 3.0% vs. 2.9 ± 1.1%, p = 0.007), while the percentage of TIGIT+ cells of CD4+ FoxP3+ T cells was significantly lower in pSjS group (0.6 ± 0.4% vs. 2.6 ± 2.4%, p = 0.013, respectively). The MFI of PD-1, CTLA-4, LAG-3, and TIM-3 in CD4+ FoxP3+ T cells was significantly higher in pSjS group when compared to HCs (1324 ± 493 vs. 753 ± 272, p < 0.001; 59 ± 18 vs. 31 ± 9, p < 0.001; 33 ± 16 vs. 24 ± 11, p = 0.008; 107 ± 20 vs. 68 ± 11, p < 0.001). Further analysis showed that, upon stimulation with PMA/ionomycin in vitro, the frequency of IFN-γ+, IL-4+ cells, and IL-17A+ cells, but not IL-10 + cells, was significantly higher in pSjS patients compared to HCs (61.9 ± 17.4% vs. 17.9 ± 5.9%, p < 0.001; 68.5 ± 18.1% vs. 18.4 ± 4.5%, p < 0.001; 61.4 ± 21.3% vs. 16.9 ± 5.3%, p = 0.001; 98.3 ± 3.1% vs. 98.1 ± 2.0%, p = 0.549, respectively).

Conclusion: These findings implied that Tregs in pSjS exhibit a more significant dysregulation than HCs and may contribute the pathogenesis.

REFERENCES: [1] Mariette, X., & Criswell, L. A. (2018). Primary Sjögren’s syndrome. New England Journal of Medicine, 378(10), 931-939.

[2] Lin, J. C., Pan, K. L., Li, C. F., Lee, K. F., Lin, K. Y., Lin, K. M., & Lin, C. Y. (2023). Altered subgroups of regulatory T cells in patients with primary Sjögren’s syndrome. Heliyon, 9(5).

Acknowledgements: NIL.

Disclosure of Interests: None declared.