Upregulation of circulating soluble programmed death-1 is associated with genetic variants in patients with rheumatoid arthritis

Abstract

Event Abstract Back to Event Upregulation of circulating soluble programmed death-1 is associated with genetic variants in patients with rheumatoid arthritis Cuiping Liu1, Juean Jiang2, Li Gao2, Ting Wang2, Min Wu3, Ting Xu3 and Xueguang Zhang1* 1 The First Affiliated Hospital of Soochow University, Jiangsu Institute of Clinical Immunology, China 2 Soochow University, Medical Biotechnology Institute, China 3 The Third Affiliated Hospital of Soochow University, Department of Rheumatology, China The Programmed death 1 (PD-1) gene is a critical regulator of T-cell activation and is also an important therapeutic target for autoimmune diseases. It had been showed that the human PD-1 gene has 5 splice variants, one of which is a soluble form lacking transmembrane domains. However, little is known about the regulation and the functional properties of soluble PD-1(sPD-1) variants. To better understand how sPD-1 could be involved in autoimmunity, we set out to characterize biochemical and functional properties of sPD-1. We first developed a specific, quantitative ELISA and then used it to detect the presence sPD-1 in serum and joint fluids from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). The levels of sPD-1 occurred at high concentrations in sera and synovial fluid of RA patients and correlated with titers of rheumatoid factor,swollen joint counts and DAS28 score in RA patients. Further characterization of soluble PD-1 revealed that it could functionally block the regulatory effect of membrane-bound PD-1 on T cell activation. Next, in correlation with their inflammatory status, we identified IFN-γ,TNF-α and IL-17 as inducers of sPD-1. Finally, the PDCD1+ 6370 single polymorphisms was found as a regulator of sPD-1 levels, serum sPD-1 levels in RA patients with GG genotype were significantly higher than those in AA genotype. Takentogether, the mechanism of antagonism of the function of PD-1 by soluble PD-1 may have important clinical relevance in the understanding of RA pathology. Acknowledgements This study was supported by the National Natural Science Foundation of China (Grants: 30930085,81001337 , 31170834). Keywords: soluble PD-1, costimulatory molecule, SNP, Autoimmunity, ra Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: Liu C, Jiang J, Gao L, Wang T, Wu M, Xu T and Zhang X (2013). Upregulation of circulating soluble programmed death-1 is associated with genetic variants in patients with rheumatoid arthritis. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00857 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 25 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Prof. Xueguang Zhang, The First Affiliated Hospital of Soochow University, Jiangsu Institute of Clinical Immunology, Suzhou, Please Select, 215006, China, xueguangzh@yahoo.com.cn Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Cuiping Liu Juean Jiang Li Gao Ting Wang Min Wu Ting Xu Xueguang Zhang Google Cuiping Liu Juean Jiang Li Gao Ting Wang Min Wu Ting Xu Xueguang Zhang Google Scholar Cuiping Liu Juean Jiang Li Gao Ting Wang Min Wu Ting Xu Xueguang Zhang PubMed Cuiping Liu Juean Jiang Li Gao Ting Wang Min Wu Ting Xu Xueguang Zhang Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.