151. Autoantibodies against aquaporin-5, a novel biomarker of primary Sjögren's syndrome
- Author
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Sung-Hwan Park, Jehan Alam, Kyungpyo Park, Jung Hee Koh, Youngnim Choi, Yeong Wook Song, S.-K. Kwok, and Nahyun Kim
- Subjects
chemistry.chemical_classification ,Transmembrane domain ,Chemistry ,IgG binding ,Genetics ,Extracellular ,Autoantibody ,Biomarker (medicine) ,IIf ,Peptide ,Molecular biology ,Genetics (clinical) ,Epitope - Abstract
The pathophysiology of exocrine dysfunction observed in Sjogren's syndrome (SS) is not fully understood. We identified autoantibodies against human AQP5 in the sera of primary SS patients. The screening of 53 control and 112 SS samples by an indirect immunofluorescence (IIF) 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. Subsequently, epitope analysis of the anti-AQP5 autoantibodies was performed by IIF assay in the presence or absence of peptides corresponding to the second transmembrane helix and extracellular loops A, C and E of AQP5. Overall, SS samples (n = 27) were inhibited by peptides corresponding to A, C, and E by approximately 40 to 50%, whereas control samples (n = 14) were inhibited only by peptides corresponding to E by less than 20%. A cyclized peptide mimicking E(E1) was most frequently recognized and best differentiated between SS and control samples. To determine functional epitopes, the effects of purified IgG and neutralizing peptides on the transepithelial osmotic permeability (PfT) of MDCK cells expressing AQP5 were measured. Incubation of MDCK-AQP5 cells with SS-, but not with control-IgG, significantly decreased PfT, which was reversed by the neutralization of IgG binding to any of the extracellular loops. In conclusion, antiAQP5 autoantibodies may be a potential biomarker and therapeutic target in SS.
- Published
- 2018