Department of Clinical Immunology, State Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, 17 Changlexi Street, Xi'an 710032, Shaanxi, PR China.
Arthritis Res Ther. 2009 Jan 9;11(1):R4. doi: 10.1186/ar2588.
The local production of pathogenic autoantibodies by plasma cells in synovium is one of the hallmarks of rheumatoid arthritis (RA). There may be a potential link between ectopic lymphoid neogenesis and the local autoimmunity in rheumatoid synovium. The unfolded protein response (UPR) has key roles in the development and maintenance of plasma cells secreting immunoglobulin. This study was designed to explore the potential links between the activation of the UPR of infiltrating plasma cells in inflamed peripheral joints and the histopathological variants of rheumatoid synovitis as well as the local production of pathogenic autoantibodies.
The variants of rheumatoid synovium were histopathologically classified into follicular and diffuse synovitis. Immunohistochemical and double-immunofluorescent stainings were performed to detect the expression of 78-kDa glucose-regulated protein (GRP78), a marker of activation of the UPR, in infiltrating plasma cells of synovium, and flow cytometry and immunoblotting analyses were performed to quantify GRP78 in plasma cells of synovial fluid in inflamed peripheral joints of RA. The detections were also taken in osteoarthritis (OA) as controls. The synovial fluid levels of anti-cyclic citrullinated peptide antibodies (anti-CCP) (IgG) were quantified with the enzyme-linked immunosorbent assay and corrected to those of total IgG in RA.
Expressions of GRP78 were more intensive in infiltrating plasma cells in RA synovium relative to those in OA synovium (P < 0.001) and in synovium with follicular synovitis relative to that with diffuse synovitis (P < 0.001). Analyses by flow cytometry and immunoblotting showed that there was a significant upregulation of GRP78 of plasma cells from synovial fluid of RA compared with that of OA (P < 0.05) and from synovial fluid of follicular synovitis relative to that of diffuse synovitis (P < 0.05). Moreover, a positive relationship between the expression of GRP78 of plasma cells from synovial fluid and the corrected synovial levels of anti-CCP (IgG) was seen in RA (P < 0.001).
There may be a link between enhanced activation of the UPR of plasma cells and ectopic lymphoid neogenesis as well as the local production of anti-CCP (IgG) in inflamed peripheral joints of RA.
浆细胞在滑膜中产生致病性自身抗体是类风湿关节炎（RA）的标志之一。异位淋巴样组织的新生与类风湿关节炎滑膜中的局部自身免疫之间可能存在潜在联系。未折叠蛋白反应（UPR）在浆细胞发育和维持分泌免疫球蛋白中起关键作用。本研究旨在探讨炎症性外周关节浸润性浆细胞 UPR 的激活与类风湿关节炎滑膜的组织病理学变异以及致病性自身抗体的局部产生之间的潜在联系。
对类风湿关节炎滑膜的组织病理学变异进行分类，分为滤泡性和弥漫性滑膜炎。通过免疫组化和双重免疫荧光染色检测滑膜浸润性浆细胞中 78kDa 葡萄糖调节蛋白（GRP78）的表达，GRP78 是 UPR 激活的标志物，并通过流式细胞术和免疫印迹分析检测炎症性外周关节滑液中浆细胞的 GRP78。还在骨关节炎（OA）中进行了检测作为对照。用酶联免疫吸附试验检测滑液中抗环瓜氨酸肽抗体（抗-CCP）（IgG）的水平，并校正为 RA 中总 IgG 的水平。
RA 滑膜浸润性浆细胞中 GRP78 的表达强度明显高于 OA 滑膜（P<0.001），且滤泡性滑膜炎的表达强度明显高于弥漫性滑膜炎（P<0.001）。流式细胞术和免疫印迹分析显示，RA 滑液中浆细胞的 GRP78 显著上调，与 OA 相比（P<0.05），与弥漫性滑膜炎相比（P<0.05），滤泡性滑膜炎的浆细胞中 GRP78 也显著上调。此外，RA 中滑膜液浆细胞 GRP78 的表达与校正后的抗-CCP（IgG）滑膜水平呈正相关（P<0.001）。
RA 炎症性外周关节中浆细胞 UPR 的激活增强可能与异位淋巴样组织的新生以及抗-CCP（IgG）的局部产生有关。
Zotero 插件
