title: Detection of autoantibodies against aquaporin-5 in the sera of patients with primary Sjögren's syndrome.
abstract: The pathophysiology of exocrine dysfunction observed in Sjögren's syndrome (SS) is not fully understood. The purpose of this study was to investigate whether autoantibodies against human AQP5 are present in the sera of SS patients. Frozen sections of mouse submandibular salivary glands, CHO cells over-expressing a human AQP5-GFP fusion protein or GFP, and MDCK cells over-expressing AQP5 were used in the indirect immunofluorescence assay to detect anti-AQP5 autoantibodies in the sera from patients with primary SS. The lysates of HEK-293 cells over-expressing the AQP5-GFP fusion protein or GFP were used for immunoprecipitation. Serum IgG from the SS patients but not from the control subjects stained acinar cells in the mouse salivary glands, the signals of which colocalized with those of AQP5-specific antibodies. Serum IgG from the SS patients also selectively stained AQP5-GFP expressed in CHO cells. However, both the control and SS sera immunoprecipitated the AQP5-GFP, suggesting that autoantibodies against AQP5 were also present in the control sera. The screening of 53 control and 112 SS samples by indirect immunofluorescence assay using the AQP5-expressing MDCK cells revealed the presence of significantly higher levels of anti-AQP5 IgG in the SS samples than in the control samples with sensitivity of 0.73 and a specificity of 0.68. Furthermore, the presence of anti-AQP5 autoantibodies was associated with low resting salivary flow in SS patients. In conclusion, anti-AQP5 autoantibodies were detected in the sera from SS patients, which could be a novel biomarker of SS and provide new insight into the pathogenesis of SS.
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
authors.forename: Jehan
authors.initials: J
authors.lastname: Alam
authors.affiliation: Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Koh
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
authors.forename: Nahyun
authors.initials: N
authors.lastname: Kim
authors.affiliation: Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Seung-Ki
authors.initials: SK
authors.lastname: Kwok
authors.affiliation: Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.affiliation: College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Yeong Wook
authors.initials: YW
authors.lastname: Song
authors.affiliation: Department of Oral Physiology, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors.forename: Kyungpyo
authors.initials: K
authors.lastname: Park
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. youngnim@snu.ac.kr.
authors.forename: Youngnim
authors.identifier: 0000-0002-6496-5560
authors.initials: Y
authors.lastname: Choi
mesh_terms: D061354:Acinar Cells / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D051402:Aquaporin 5 / Q000276:immunology / Q000378:metabolism*; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D004285:Dogs; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008875:Middle Aged; D012469:Salivary Glands / Q000473:pathology; D012859:Sjogren's Syndrome / Q000175:diagnosis / Q000276:immunology*; D055815:Young Adult
chemical_list: D051402:Aquaporin 5; D001323:Autoantibodies; D015415:Biomarkers
keywords: Autoimmune disease; Biomarkers; Exocrine dysfunction; Indirect immunofluorescence assay; Sensitivity and specificity; Xerostomia