Detection of Citrullinated Fibrin in Plasma Clots of Rheumatoid Arthritis Patients and Its Relation to Altered Structural Clot Properties, Disease-Related Inflammation and Prothrombotic Tendency.
Detection of Citrullinated Fibrin in Plasma Clots of Rheumatoid Arthritis Patients and Its Relation to Altered Structural Clot Properties, Disease-Related Inflammation and Prothrombotic Tendency.
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DOI：
10.3389/fimmu.2020.577523
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发表时间：
2020
影响因子：
7.3
通讯作者：
Pretorius E
中科院分区：
文献类型：
--
作者：
Bezuidenhout JA;Venter C;Roberts TJ;Tarr G;Kell DB;Pretorius E
风湿性关节炎（RA）患者发生心血管事件的风险由于全身炎症而不成比例地升高。自身免疫相关瓜氨酸对纤维蛋白（原）的结构和血栓形成潜力的相对影响尚不清楚。因此，我们比较了RA患者与健康对照组的血管功能、炎症、凝血和纤维蛋白凝块组成的指数，并评估了与疾病存在的参数相关性。从30名RA患者和30名年龄和性别匹配的健康志愿者中收集血液样本。采用双抗体夹心法检测血清淀粉样蛋白A（SAA）、C反应蛋白（CRP）、可溶性细胞间粘附分子1（sICAM-1）和可溶性血管细胞粘附分子1（sVCAM-1）水平。使用血栓弹力图（TEG®）评估全血凝固。使用扫描电子显微镜研究纤维凝块网络和纤维结构。使用荧光标记的瓜氨酸单克隆抗体和荧光宽视野显微镜对形成的纤维蛋白凝块中的瓜氨酸进行检测和定量。RA患者血清SAA、CRP和ICAM-1浓度均显著高于对照组。在RA患者中，与凝血起始、纤维蛋白交联速率和达到最大血栓生成时间相关的TEG参数减弱。显微镜分析显示，与对照组相比，RA患者中存在较厚纤维蛋白纤维的密集网络，并且RA患者中存在纤维蛋白凝块结构内的多个瓜氨酸化区域。我们的研究结果提供了新的证据，证明与对照血浆相比，血管内纤维蛋白的瓜氨酸在RA血浆中更突出，并且血浆比滑液更易接近。瓜氨酸化纤维蛋白原可能作为RA患者血栓形成风险的决定因素发挥作用。
The risk of cardiovascular events in patients with Rheumatoid Arthritis (RA) is disproportionately heightened as a result of systemic inflammation. The relative effect of autoimmune-associated citrullination on the structure and thrombotic potential of fibrin(ogen) remains unknown. We therefore compared indices of vascular function, inflammation, coagulation and fibrin clot composition in RA patients with healthy controls and evaluated parameter association with disease presence. Blood samples were collected from 30 RA patients and 30 age- and gender-matched healthy volunteers. Levels of serum amyloid A (SAA), c-reactive protein (CRP), soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1) was measured using a sandwich immunoassay. Whole blood coagulation was assessed using Thromboelastography (TEG®). Fibrin clot networks and fiber structure was investigated using Scanning Electron Microscopy. The detection and quantification of citrullination in formed fibrin clots was performed using a fluorescently labeled Citrulline monoclonal antibody with Fluorescence Wide Field Microscopy. Concentrations of SAA, CRP and ICAM-1 were significantly elevated in RA patients compared to controls. TEG parameters relating to coagulation initiation, rate of fibrin cross-linking, and time to reach maximum thrombus generation were attenuated in RA patients. Microscopic analysis revealed denser networks of thicker fibrin fibers in RA patients compared to controls and multiple citrullinated regions within fibrin clot structures in RA patients were present. Our findings provide novel evidence for the citrullination of fibrin within vasculature is more prominent in RA plasma compared to control plasma and plasma is more accessible than synovial fluid. Citrullinated fibrinogen could play a role as a determinant of thrombotic risk in RA patients.
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影响因子：
5.7
作者：
Litvinov, Rustem I.;Weisel, John W.
通讯作者：
Weisel, John W.
DOI：
10.4049/jimmunol.1201517
发表时间：
2013-02-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cordova KN;Willis VC;Haskins K;Holers VM
通讯作者：
Holers VM
影响因子：
5.7
作者：
Bisoendial, Radjesh J.;Levi, Marcel;Stroes, Eric S. G.
通讯作者：
Stroes, Eric S. G.
影响因子：
3.7
作者：
Bucay, Igal;O'Brien, E. Tim, III;Hudson, Nathan E.
通讯作者：
Hudson, Nathan E.
影响因子：
4
作者：
Kern, Anita;Balog, Attila;Vasarhelyi, Barna
通讯作者：
Vasarhelyi, Barna