Ab0812 the Role of Chemokines Cxcl9, Cxcl10, Cxcl11, and Cxcr3 in the Serum and Minor Salivary Gland Tissues of Patients With Sjögren’s Syndrome

Background: The chemokines C-X-C motif chemokine ligands (CXCL) 9, CXCL10, CXCL11, known for their function in coordinating directional migration of CD4+ TH1 cells, CD8+ T cells, NK cells, and NKT cells through interaction with their mutual receptor CXC chemokine receptor 3 (CXCR3), are implicated in various pathophysiological processes of autoinflammation and autoimmune diseases. However, their specific roles in Sjögren's syndrome, an autoimmune disorder, have not been well elucidated. Objectives: This study aimed to investigate serum levels and expression levels in minor salivary glands (MSG) of CXCL9, CXCL10, CXCL11, and CXCR3 in patients with primary Sjögren's syndrome (pSS) and validate their clinical utility by exploring potential correlations with clinical parameters. Methods: Serum samples were collected from 49 patients diagnosed with pSS for the measurement of CXCL9, CXCL10, CXCL11, and CXCR3. As a control group, serum samples were obtained from 33 patients with rheumatoid arthritis (RA) and 30 healthy controls (HC). CXCL levels in MSG tissue were measured from 41 patients who underwent MSG biopsy. All specimens underwent leukocyte common antigen staining for inflammation infiltration assessment, and focus scores were calculated by the pathologist. Correlations between CXCL/CXCR levels in serum/MSG tissues and clinical factors/salivary scintigraphy parameters were analyzed. Results: The mean age of pSS patients was 47.6 year, with 95.9% being female, showing no significant difference compared to the control groups. The mean EULAR SS disease activity index (ESSDAI) score was 3.67. Serum CXCL11 and CXCR3 showed statistically significant differences among the pSS, RA, and HCs (serum CXCL11, pSS:RA:HC = 235.6 ± 500.1 pg/mL: 90.0 ± 200.3 pg/mL: 45.9 ± 53.6 pg/mL; p = 0.041, serum CXCR3, pSS:RA:HC = 3.27 ± 1.32 pg/mL: 3.29 ± 1.17 pg/mL: 2.00 ± 1.12 pg/mL; p <0.001). Serum CXCL10 showed a statistically significant difference between pSS (64.5 ± 54.2 pg/mL) and HCs (18.6 ± 18.1pg/mL), while serum CXCL9 did not exhibit a significant difference among the groups. Correlation analysis with clinical factors revealed that serum CXCL10 and CXCL11 had positive correlations with ESR (r = 0.524, p <0.001 and r = 0.707, p <0.001), total protein (r = 0.375, p = 0.008 and r = 0.535, p <0.001), globulin (r = 0.539, p <0.001 and r = 0.639, p <0.001), and ESSDAI (r = 0.305, p = 0.033 and r = 0.321, p = 0.025). Additionally, serum CXCL10 showed a negative correlation with the Schirmer test (r = -0.354, p = 0.05), while serum CXCL11 exhibited a positive correlation with biopsy focus score (r = 0.612, p = 0.02). In MSG tissue, the percentage of infiltrating CXCL9-positive cell was highest at 75.5%, followed by CXCL10 at 29.1%, and CXCL11 at 27.9%. Conclusion: Our study indicates that the CXCL9, CXCL10, CXCL11/CXCR3 axis may contribute to the clinical symptoms and histological characteristics of pSS. REFERENCES: [1] Dillemans L, Somer LD, Neerinckx B, Proost P. A review of the pleiotropic actions of the IFN-inducible CXC chemokine receptor 3 ligands in the synovial microenvironment. Cell Mol Life Sci. 2023;80:78. [2] Chatzis L, Goules AV., Stergiou IE., Voulgarelis M, Tzioufas AG., Kapsogeorgou EK. Serum, but Not Saliva, CXCL13 Levels Associate With Infiltrating CXCL13+ Cells in the Minor Salivary Gland Lesions and Other Histologic Parameters in Patients With Sjögren's Syndrome. Front Immunol. 2021:12:705079. [3] Yoon K-C, Park C-S, You I-C, Choi H-J, Lee K-H, Im S-K, et al. Expression of CXCL9, -10, -11, and CXCR3 in the tear film and ocular surface of patients with dry eye syndrome. Invest Ophthalmol Vis Sci. 2010;51:643-50. Acknowledgements: NIL. Disclosure of Interests: None declared.