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      Associations of Anti-Aquaporin 5 Autoantibodies with Serologic and Histopathological Features of Sjögren’s Syndrome

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          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.

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          Most cited references17

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          Prediction of Sjögren's Syndrome Years Before Diagnosis and Identification of Patients With Early Onset and Severe Disease Course by Autoantibody Profiling.

          Autoantibodies are highly characteristic of primary Sjögren's syndrome (SS) and represent important tools for studying its pathogenesis. Nonetheless, thus far, no systematic investigations have assessed the presence of autoantibodies before diagnosis. This study was undertaken to analyze how early and in what order autoantibodies appear, how predictive they are of primary SS, and whether they identify disease subsets.
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            Evaluation of aquaporin-4 antibody assays.

            Aquaporin-4 (AQP4) is a water channel protein that is most highly, but not exclusively, expressed in the central nervous system. In 2005 AQP4 was shown to be the antigenic target of neuromyelitis optica-immunoglobulin G (NMO-IgG, or AQP4-IgG), an antibody found specifically in patients with NMO and in formes frustes of NMO, such as longitudinally extensive transverse myelitis (LETM) or optic neuritis (ON). This discovery facilitated the clinical, pathological, and radiological distinction of NMO and the spectrum of NMO-related disorders from classical multiple sclerosis. In addition to its use as a diagnostic tool, AQP4-IgG predicts a high risk of relapse in patients with a clinically isolated syndrome of either LETM or ON. As disability in NMO is attack-related, early diagnosis and treatment are predicted to have a major effect on long-term disability. Thus, the importance of sensitive and specific assays to detect AQP4-IgG cannot be overstated. Both academic institutions and commercial companies have developed assays to identify AQP4-IgG in patients' sera or cerebrospinal fluid. Both AQP4 isoforms from different species have been used as the antigenic target in the form of frozen tissue sections in indirect immunofluorescence assays, partially purified protein for fluorescence immunoprecipitation assay, radioimmunoprecipita-tion assay or enzyme-linked immunosorbent assay, or transfected into cells for cell based assays or flow cytometry. We carried out a systematic review of the literature reporting different methodologies used to identify AQP4-IgG, examine whether longitudinal AQP4-IgG titers predict relapses in seropositive patients, and attempt to establish a reasonable timeframe for retesting negative serum samples.
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              Aquaporin-5: from structure to function and dysfunction in cancer.

              Aquaporins, a highly conserved group of membrane proteins, are involved in the bidirectional transfer of water and small solutes across cell membranes taking part in many biological functions all over the human body. In view of the wide range of cancer malignancies in which aquaporin-5 (AQP5) has been detected, an increasing interest in its implication in carcinogenesis has emerged. Recent publications suggest that this isoform may enhance cancer cell proliferation, migration and survival in a variety of malignancies, with strong evidences pointing to AQP5 as a promising drug target and as a novel biomarker for cancer aggressiveness with high translational potential for therapeutics and diagnostics. This review addresses the structural and functional features of AQP5, detailing its tissue distribution and functions in human body, its expression pattern in a variety of tumors, and highlighting the underlying mechanisms involved in carcinogenesis. Finally, the actual progress of AQP5 research, implications in cancer biology and potential for cancer detection and prognosis are discussed.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                03 November 2019
                November 2019
                : 8
                : 11
                Affiliations
                [1 ]Department of Immunology and Molecular Microbiology, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehak-ro, Seoul 03080, Korea; pinkngold@ 123456naver.com
                [2 ]Division of Rheumatology, Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, 222, Banpo-daero, Seoul 06591, Korea; poohish@ 123456naver.com (J.L.); rapark@ 123456catholic.ac.kr (S.-H.P.)
                [3 ]Department of Preventive and Social Dentistry, School of Dentistry, Seoul National University, 101 Daehak-ro, Seoul 03080, Korea; hyundkim@ 123456snu.ac.kr
                Author notes
                [* ]Correspondence: youngnim@ 123456snu.ac.kr
                Article
                jcm-08-01863
                10.3390/jcm8111863
                6912604
                31684196
                279b7b7a-92b3-4f6b-9c19-74388b9163f9
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                Categories
                Article

                sjogren syndrome,autoantibody,aquaporin 5,epitope,cell-based immunofluorescence cytochemistry,elisa

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