Abstract
Biomarkers to stratify the complex and heterogeneous phenotypes of Sjogren’s syndrome (SS) are needed. We aimed to validate the prevalence of anti-aquaporin 5 (AQP5) IgG in a non-Korean cohort and to optimize the method to screen the anti-AQP5 IgG. The study cohort included 111 primary SS and 43 non-SS Sjögren’s International Collaborative Clinical Alliance (SICCA) controls that were obtained from the Sjögren’s International Collaborative Clinical Alliance registry, in addition to 35 systemic lupus erythematosus (SLE) and 35 rheumatoid arthritis (RA) phenotypes. Anti-AQP5 IgG was screened by cell-based immunofluorescence cytochemistry (CB-IFC) assay in the absence or presence of epitope peptides, as well as by ELISA using the epitope peptides as coated antigens. Anti-AQP5 IgG specific to an E1 epitope was best at discriminating between SS and non-SS, and the two different methods (CB-IFC and ELISA) presented comparable performance in diagnostic accuracy (0.690 vs. 0.707). Notably, the SLE and RA groups had substantially lower levels of anti-AQP5 IgG than the SS group. In addition, the presence of anti-AQP5_E1 IgG was associated with serologic and histopathological features of SS. In conclusion, a similar prevalence of anti-AQP5 IgG was confirmed in a non-Korean cohort. Screening anti-AQP5 autoantibodies may help to form subgroups of SS for targeted therapy.
Highlights
Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by a dry mouth, dry eyes, and focal lymphocytic infiltration of the salivary/lacrimal glands [1]
Due to the fact that all used samples were from tissue banks, a written informed consent for the current study was waivered. For this case-control study, 154 serum samples of Asian females, including 111 primary SS patients and 43 non-SS controls, all of whom had signs and symptoms suggestive of SS, were obtained from Sjögren’s International Collaborative Clinical Alliance (SICCA) registry
The presence of anti-aquaporin 5 (AQP5) immunoglobulin G (IgG) was determined by cell-based immunofluorescence cytochemistry (CB-IFC) using a 1:100 dilution of sera and Madin-Darby canine kidney (MDCK)-AQP5 cells
Summary
Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by a dry mouth, dry eyes, and focal lymphocytic infiltration of the salivary/lacrimal glands [1]. We previously reported the presence of anti–AQP5 immunoglobulin G (IgG) in Korean patients with primary SS with a sensitivity of 0.73 and a specificity of 0.68 [11]. We characterized the epitopes of anti-AQP5 IgG localized to the three extracellular loops [12]. To serve as the biomarker of SS, the validation of anti-AQP5 IgG and its assay method is important. The aims of this study were to validate the prevalence of anti-AQP5 IgG in a non-Korean cohort and to optimize the method for the detection of anti-AQP5 IgG. We report the presence of anti-AQP5 autoantibodies in a non-Korean cohort and strong associations of the anti-AQP5 autoantibodies with serologic and histopathological features of SS
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