Antibodies to aquaporins are frequent in patients with primary Sjögren's syndrome

Abstract

Objectives: Several aquaporins (AQPs) are present in the salivary glands, likely contributing to their secretions. AQP dysfunction may contribute to the salivary gland dysfunction in SS. Antibodies to AQP4 and AQP1 are detected in neuromyelitis optica and are believed to play a pathogenic role. We aimed to search for antibodies to several AQPs in the sera from SS patients in an effort to shed light on the pathogenic mechanisms of SS.

Methods: We searched for antibodies to six AQPs in the sera of 34 SS patients without neurological findings using ELISAs with synthetic peptides corresponding to the three extracellular domains of each AQP, radioimmunoassays with AQPs, Western blots and competition experiments with cell-embedded AQPs.

Results: Thirteen (38.2%) SS patients had antibodies to extracellular domains of AQP1 (two), AQP3 (one), AQP8 (six) or AQP9 (four); none had AQP4 or AQP5 antibodies. Each patient had antibodies to only one extracellular domain. AQP binding was further verified by radioimmunoassay with intact AQPs, western blots and AQP-transfected cells. In contrast, none of the 106 healthy controls or 68 patients with other autoimmune diseases had antibodies to intact AQPs. Expression of AQP8 (the major antibody target) on human salivary glands was shown by immunohistochemistry. Patients with anti-AQP antibodies had more severe xeropthalmia compared with anti-AQP-negative patients, suggesting a potential pathogenic role of these antibodies.

Conclusion: Antibodies to AQPs (especially to AQP8 and AQP9) are frequent in SS patients. The likely important role of AQPs in salivary gland secretions justifies further research.

Keywords: Sjögren’s syndrome; aquaporins; autoantibodies; autoimmune disease; biomarkers.