Primary Sjögren's Syndrome: Rituximab Restores Salivary Gland Structure and Function

Objectives: To investigate the efficacy of the anti-CD20 antibody rituximab on the immune-mediated inflammatory changes in labial salivary gland tissue and on the salivary gland function in patients with primary Sjögren's syndrome. Methods: In this open-label study including 20 female patients (mean age 48 ±15 years) with primary Sjögren's syndrome fulfilling the revised American-European Consensus Group Criteria, unstimulated and chewing-stimulated whole saliva and stimulated parotid saliva flow rates were measured and labial salivary gland biopsies obtained before and 195 days after treatment with rituximab (infusion of 1,000 mg on days 1 and 15). The biopsies were routinely processed, embedded in paraffin wax and stained with haematoxylin/eosin. B- and T-lymphocyte distribution was analysed using immunohistochemistry. Also the relative amount of salivary gland parenchyma and lymphocytic inflammation was assessed. Results: At baseline, labial salivary gland biopsies revealed focal periductal lymphocytic infiltrates in all patients (mean focus score 3.7; range 1-12). After treatment, the extent and amount of lymphocytic infiltrates, including germinal centers, decreased in 60% of the patients (focus score: 1.9; 0-12, p=0.02) Also the relative amount of acinar and fat tissue increased and the relative number of B-cells and plasma cells decreased after treatment. Unstimulated and chewing-stimulated whole and parotid saliva flow rates increased in 65%, 60% and 70% of the patients, respectively (mean increase from baseline: 39%, 21% and 18% (p=0.03, p=0.001 and p=0.02, respectively). The improvement of salivary gland function did not correlate to the reduction in focal lymphocytic infiltration nor to age or duration of disease. Conclusion: Our results indicate that B-cell depletion with rituximab can attenuate the immune-mediated inflammatory changes in labial salivary gland and independently hereof improve salivary gland function in terms of whole and parotid saliva flow rates in the majority of patients with primary Sjögren's syndrome, and presumably postpone the progression of the disease.