High levels of soluble GPR56/ADGRG1 are associated with positive rheumatoid factor and elevated tumor necrosis factor in patients with rheumatoid arthritis |
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Authors: | Wen-Yi Tseng Yeong-Jian Jan Wu Tai-Yun Yang Nien-Yi Chiang Wen-Pin Tsai Siamon Gordon Gin-Wen Chang Chang-Fu Kuo Shue-Fen Luo Hsi-Hsien Lin |
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Affiliation: | 1. Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital-Keelung, Keelung, Taiwan;2. Kennedy Institute of Rheumatology, University of Oxford, OX3 7FY, Oxford, UK;3. Department of Medicine, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan;4. Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan;5. Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan;6. Sir William Dunn School of Pathology, University of Oxford, OX1 3RE, Oxford, UK;7. Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital-Linkou, Tao-Yuan, Taiwan;8. Department of Anatomic Pathology, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan;9. Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Tao-Yuan, Taiwan |
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Abstract: | BackgroundGPR56/ADGRG1 is a member of the adhesion-class G protein-coupled receptor (aGPCR) family important in brain development, oncogenesis and tumor metastasis. Like other aGPCRs, GPR56 is cleaved at the GPCR proteolysis site (GPS) motif into an N-terminal fragment (NTF) and a C-terminal fragment (CTF). Existence of soluble GPR56 (sGPR56) has been shown in vitro, however the underlying mechanism and its pathophysiologic role remains undetermined.ObjectiveTo assess the presence of sGPR56 in human serum using ELISA assay and compare the serum sGPR56 levels among patients of various chronic inflammatory diseases and healthy subjects.Patients and methodsIn this study, serum samples from patients with systemic lupus erythematosus (SLE) (n = 57), rheumatoid arthritis (RA) (n = 95), Sjögren's syndrome (SS) (n = 29), ankylosing spondylitis (AS) (n = 51), and normal controls (n = 81) were analyzed using sGPR56-specific ELISA.ResultWe show that serum sGPR56 levels are increased in patients of RA, but not in those with SLE, SS and AS. Intriguingly, serum sGPR56 levels in RA patients correlated with positive rheumatoid factor, a marker of bone erosion and poor outcome. In addition, an elevated sGPR56 level is also noted in RA patients with higher tumor necrosis factor level.Conclusionwe conclude that sGPR56 is present in vivo and sGPR56 level is elevated in certain chronic inflammatory diseases such as RA. Hence, sGPR56 might be considered a potential biomarker for RA disease progression. |
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Keywords: | Adhesion-GPCR Biomarker sGPR56 Shedding RA AS ankylosing spondylitis ECD extracellular domain ELISA the enzyme-linked immunosorbent assay GPCR G protein-coupled receptor GPS GPCR proteolysis site MMP matrix metalloproteinase NSAIDs non-steroid anti-inflammatory drugs RA rheumatoid arthritis RF rheumatoid factor sGPR56 soluble GPR56 protein SLE systemic lupus erythematosus SS Sjögren's syndrome TNF-α tumor necrosis factor-α |
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