Identification of autoantibodies to aquaporin-5 in sera from patients with Sjögren’s syndrome

Sjögren’s syndrome (SS) is an autoimmune disorder that primarily targets the salivary and lacrimal glands, leading to dryness of the mouth and eye. Although anti-muscarinic receptor 3 autoantibodies have been shown to inhibit the function of acinar cells, the pathophysiology of exocrine dysfunction in SS is not fully understood. Aquaporin-5 (AQP5), a water-channel protein expressed at the acinar cells of the lacrimal and salivary glands, plays a critical role in tear and saliva secretion. Many oral bacterial species express AQPs that have high levels of homology with human AQP5. Therefore, we hypothesized that SS patients may have autoantibodies to AQP5 in sera. To test our hypothesis, the sections of mouse submandibular salivary gland were dual stained with anti-AQP5 antibody and either control or SS patient sera. The signals of AQP5 expressed in the mucous acini, serous acini, and ductal areas showed strong co-localization with the signals stained with SS patient IgG but control sera did not stain the sections. Sera from SS patients, but not from control subjects, also selectively stained the AQP5-EGFP overexpressed in CHO cells. Although both the SS and control sera immuneprecipitated AQP5-EGFP, blind screening of MDCK cells overexpressing AQP5 by immunofluorescence assay revealed that 3 out of 10 SS patients contained higher levels of anti-AQP5 IgG than control subjects. In conclusion, the anti-AQP5 autoantibodies detected in SS sera may be a useful disease biomarker.