Distinct tear cytokine profile and ocular surface phenotype in primary biliary cholangitis patients with Sjögren's syndrome

To compare the ocular surface phenotype and tear cytokine profile of primary biliary cholangitis (PBC) patients with and without concomitant Sjögren's syndrome (SS).

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.

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).

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.