Original Article

The immunoglobulin D Fc receptor expressed on fibroblast-like synoviocytes from patients with rheumatoid arthritis contributes to the cell activation

Authors: WU Yu-jing, CHEN Wen-sheng, CHEN Heng-shi, DAI Xing, DONG Jin, WANG Ying, ZHANG Ling-ling, CHANG Yan, HUANG Qiong, JIA Xiao-yi, WEI Wei
Corresponding to: WU Yu-jing
DOI: 10.1038/aps.2017.105

Abstract

Immunoglobulin IgD might play an important role in autoimmune diseases, but the function of IgD has remained elusive, despite multiple attempts to define its biological function. Fibroblast-like synoviocytes (FLSs) are specialized cells of the synovium that play a key role in the pathogenesis of rheumatoid arthritis (RA). In this study we explored the possible roles of excessive IgD expression on the function of FLSs from RA patients (RA-FLSs). We showed that IgD Fc receptor (IgDR) was constitutively expressed on FLSs, and was significantly elevated in RA-FLSs compared with FLSs prepared from synovial tissues of healthy controls (HC-FLSs). Furthermore, IgDR was mainly detected on the cell surface and in the cytoplasm. We further detected the intrinsic binding affinity of IgD to IgDR on HC-FLSs with an equilibrium dissociation constant (KD) of 0.067 nmol/L. Incubation of RA-FLSs with IgD (1–10 μg/mL) for 48 h dosedependently promoted the expression of IgDR, and stimulated the production of inflammatory cytokines and chemokines, such as IL-1β, IL-6, monocyte chemotactic protein (MCP)-1, TNF-α and receptor activator of nuclear factor-κB ligand (RANKL), thus potentially contributing to IgD-IgDR crosslinking. Moreover, incubation with IgD (0.1–10 μg/mL) for 48 h dose-dependently enhanced viability for both HC-FLSs and RA-FLSs. Our results demonstrate that IgDR is expressed on RA-FLSs and contributes to the activation of FLSs, and suggest that IgD-IgDR is a potential novel immunotherapeutic target for the management of RA.
Keywords: rheumatoid arthritis; immunoglobulin D; immunoglobulin D Fc receptor; fibroblast-like synoviocytes; fluorescence based receptor binding assay; inflammatory cytokines