Abstract:AIM: To compare the ocular surface phenotype and tear cytokine profile of primary biliary cholangitis (PBC) patients with and without concomitant Sjögren’s syndrome (SS). METHODS: This case-control study enrolled 21 PBC patients with SS (PBC-SS group), 23 PBC patients without SS (PBC-only group), and 20 age- and sex-matched healthy controls. All participants underwent standardized ocular surface assessments including Ocular Surface Disease Index (OSDI) questionnaire, lipid layer thickness (LLT), incomplete blink rate, tear meniscus height (TMH), non-invasive tear film breakup time (NIBUT), meibomian gland loss (MGL), Schirmer I test, and corneal fluorescein staining (CFS). Tear concentrations of six cytokines [interleukin (IL)-6, IL-8, IL-10, vascular cell adhesion molecule-1 (VCAM-1), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF)] were measured using a customized ultra-sensitive quantitative antibody array (QAA-CUST) platform. RESULTS: The three groups were comparable in terms of age (54.2±8.6, 52.8±9.3, and 53.5±8.9y, respectively; P=0.873) and gender distribution (female predominance: 100%, 91.3%, and 95%; P=0.412). Compared to PBC-only patients, the PBC-SS group exhibited significantly worse ocular surface parameters, including higher OSDI scores (45.6±12.3 vs 28.4±9.7), lower Schirmer I values (3.8±2.1 vs 7.6±3.2 mm/5min), reduced TMH (0.18±0.06 vs 0.22±0.05 mm), and shorter NIBUT (4.2±1.8 vs 6.2±2.0s), all P<0.001. Both PBC groups showed reduced LLT and increased MGL compared to healthy controls (P<0.05), while CFS scores were similarly elevated in both PBC groups versus controls (P<0.001). Tear cytokine analysis revealed significantly higher levels of IL-6, IL-8, and VCAM-1, and lower levels of IL-10 in the PBC-SS group compared to the PBC-only group (all P<0.05). VEGF was elevated in both PBC groups versus controls (P<0.05). In PBC-SS patients, VCAM-1 demonstrated the strongest correlations with Schirmer I values (ρ=-0.71, P<0.001) and CFS scores (ρ=0.68, P<0.001). CONCLUSION: Compared to PBC-only patients, PBC patients with SS exhibit a distinct and more severe ocular surface phenotype characterized by pronounced aqueous tear deficiency and a unique tear inflammatory signature with elevated VCAM-1, IL-6, IL-8 and reduced IL-10. Tear cytokine profiling, particularly VCAM-1, may serve as a valuable non-invasive tool for identifying SS comorbidity in PBC patients and monitoring disease severity.
