Sjögren's Syndrome Characterization and Management

Sjögren’s syndrome is a chronic autoimmune disorder principally affecting exocrine glands, leading to persistent dryness of the eyes and mouth, and often extending to systemic complications. Lymphocytic infiltration of lacrimal and salivary glands disrupts fluid secretion, while aberrant B-cell activation and autoantibody production drive systemic manifestations such as arthralgia, fatigue and vasculitis. Diagnosis relies on a combination of clinical assessment, serological markers and salivary gland histopathology with a quantified focus score. Management encompasses symptomatic relief of sicca features through lubricants and secretagogues, immunomodulatory agents for systemic involvement and periodic screening for lymphoma risk. Emerging strategies seek to refine patient stratification, incorporate novel biomarkers and target pathogenic immune pathways to move beyond empirical therapy towards precision medicine.

Research from Nature Portfolio

A phase 2 trial of a CD40 ligand antagonist fusion protein has demonstrated statistically significant improvement in both systemic disease activity and patient-reported symptoms of Sjögren’s syndrome over a 169-day period. By disrupting costimulatory signals between T cells, B cells and antigen-presenting cells, this agent reduced established disease activity indices and was generally well tolerated. Safety outcomes mirrored those of standard care, with no unexpected toxicities. These results underscore the central role of the CD40/CD40 ligand axis in driving glandular and extraglandular autoimmunity and support further development of targeted immunotherapy as a disease-modifying approach.

Sjögren's Syndrome Characterization and Management publication trend

The graph below shows the total number of articles in sjögren's syndrome characterization and management across all publications each year (not limited to Nature Index journals).

Technical terms

Autoantibody: An antibody produced by the immune system that mistakenly targets the body’s own tissues.

CD40 ligand: A protein on activated T cells that binds CD40 on B cells and antigen-presenting cells to drive immune activation.

Focus score: A numerical measure of lymphocytic foci per 4 mm² of salivary gland tissue used in histopathological diagnosis.

Hyposalivation: Reduced saliva production leading to dry mouth and associated complications.

Tight junction: Intercellular barrier complexes in epithelial cells that regulate passage of fluids and solutes.

References

1. CD40 ligand antagonist dazodalibep in Sjögren’s disease: a randomized, double-blinded, placebo-controlled, phase 2 trial. Nature Medicine (2024).
2. TScan-II: A genome-scale platform for the de novo identification of CD4+ T cell epitopes. Cell (2023).
3. Loss of tricellular tight junction tricellulin leads to hyposalivation in Sjögren’s syndrome. International Journal of Oral Science (2025).
4. Standardisation of labial salivary gland histopathology in clinical trials in primary Sjögren's syndrome. Annals of the Rheumatic Diseases (2016).
5. Sjögren’s syndrome: a systemic autoimmune disease. Clinical and Experimental Medicine (2021).