Clinical implication and tissue-specific activation of the OX40-OX40L costimulatory pathway in Sjögren's disease.

OBJECTIVES: Sjögren's disease (SjD) is a chronic autoimmune disease characterised by immune-mediated inflammation of exocrine glands. The OX40-OX40 ligand (OX40L) costimulatory pathway plays a key role in T cell activation and persistence. However, its involvement in both systemic and tissue compartments in SjD remains incompletely understood. This study investigated the expression of the OX40-OX40L pathway in SjD and its association with clinical and immunologic features. METHODS: Serum levels of OX40 and OX40L were measured in SjD patients using enzyme-linked immunosorbent assay and compared with those in healthy controls (HCs). Associations with clinical and laboratory parameters, including disease activity indices, were analysed. Expression and spatial localisation of OX40 and OX40L in minor salivary gland biopsy specimens were assessed using immunohistochemistry and immunofluorescence. RESULTS: Serum OX40 levels were significantly elevated in SjD patients compared with HCs and were positively correlated with systemic disease activity and serum β2-microglobulin levels. Higher serum OX40 levels were observed in SjD patients with leukopenia and lymphadenopathy. In minor salivary gland tissue, both OX40 and OX40L expression increased with higher focus scores. OX40 was localised to CD4+ and CD8+ T cells, whereas OX40L was localised to glandular epithelial cells and infiltrating B cells. CONCLUSIONS: The OX40-OX40L pathway shows distinct patterns of activation in systemic and glandular immune compartments in SjD. These findings suggest its involvement in disease-related immune responses and support its relevance as a pathway of interest in SjD.