Rheumatoid Arthritis Patients With Circulating Extracellular Vesicles Positive for IgM Rheumatoid Factor Have Higher Disease Activity.
Rheumatoid Arthritis Patients With Circulating Extracellular Vesicles Positive for IgM Rheumatoid Factor Have Higher Disease Activity.
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DOI：
10.3389/fimmu.2018.02388
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发表时间：
2018
影响因子：
7.3
通讯作者：
van de Loo FAJ
中科院分区：
文献类型：
--
作者：
Arntz OJ;Pieters BCH;Thurlings RM;Wenink MH;van Lent PLEM;Koenders MI;van den Hoogen FHJ;van der Kraan PM;van de Loo FAJ
类风湿关节炎(RA)是一种主要累及滑膜关节的自身免疫性炎症性疾病。类风湿因子IgM(IgM-RF)、抗瓜氨酸蛋白自身抗体(ACPA)、C反应蛋白(CRP)水平和血沉(ESR)是类风湿因子(RA)诊断的有效实验室参数。使用的临床参数是压痛(TJC)和肿胀关节(SJC)的数量以及全球患者视觉模拟评分(VAS)。为了确定患者的疾病缓解，可以根据SJC、TJC、VAS和ESR(或替代的CRP)计算疾病活动评分(DAS28)。然而，在个体患者中跟随治疗反应而发生的细微和更好的预测性变化不能通过上述参数或通过测量血液中的细胞因子水平来衡量。由于细胞外小泡(EV)在细胞间通讯中发挥作用，并携带大量信号，我们开始确定它们作为疾病活动生物标志物的价值。用体积排阻色谱(SEC)从41例RA患者和24例健康对照(HC)的无血小板血浆中分离EVS。我们分别使用NanoSight颗粒跟踪分析和Micro-BCA对颗粒和蛋白质浓度进行了量化，并且没有观察到RA患者和HC患者之间的差异。41例RA患者中28例血浆中可检测到IgM-RF，其中13例血清阳性(RF+RA)患者的PEV上也可检测到IgM-RF(IgM-RF+)。在血清阴性的RA患者(RF、−、RA)中，我们没有在PEV上发现任何RF。当比较疾病参数时，我们发现RF+RA和RF−RA患者之间没有差异，只是RF+RA患者的血沉水平升高。而伴有IgM-RF+PEV的RF+RA患者的CRP和ESR水平显著高于无IgM-RF+PEVS的RA+RA患者，VAS和DAS28也显著高于无IgM-RF+PEV的RA+RA患者。这项研究首次表明，在部分疾病活动性较高的RF+RA患者中，PEV上存在IgM-RF。
Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that mainly affects synovial joints. Validated laboratory parameters for RA diagnosis are higher blood levels of rheumatoid factor IgM (IgM-RF), anti-citrullinated protein autoantibodies (ACPA), C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR). Clinical parameters used are the number of tender (TJC) and swollen joints (SJC) and the global patient visual analog score (VAS). To determine disease remission in patients a disease activity score (DAS28) can be calculated based on SJC, TJC, VAS, and ESR (or alternatively CRP). However, subtle and better predictive changes to follow treatment responses in individual patients cannot be measured by the above mentioned parameters nor by measuring cytokine levels in blood. As extracellular vesicles (EVs) play a role in intercellular communication and carry a multitude of signals we set out to determine their value as a biomarker for disease activity. EVs were isolated from platelet-free plasma of 41 RA patients and 24 healthy controls (HC) by size exclusion chromatography (SEC). We quantified the particle and protein concentration, using NanoSight particle tracking analysis and micro-BCA, respectively, and observed no differences between RA patients and HC. In plasma of 28 out of 41 RA patients IgM-RF was detectable by ELISA, and in 13 out of these 28 seropositive RA patients (RF+RA) IgM-RF was also detected on their isolated pEVs (IgM-RF+). In seronegative RA patients (RF−RA) we did not find any RF present on pEVs. When comparing disease parameters we found no differences between RF+RA and RF−RA patients, except for increased ESR levels in RF+RA patients. However, RF+RA patients with IgM-RF+ pEVs showed significantly higher levels of CRP and ESR and also VAS and DAS28 were significantly increased compared to RA+ patients without IgM-RF+ pEVs. This study shows for the first time the presence of IgM-RF on pEVs in a proportion of RF+RA patients with a higher disease activity.
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影响因子：
5.2
作者：
Arntz, Onno J.;Pieters, Bartijn C. H.;van de Loo, Fons A. J.
通讯作者：
van de Loo, Fons A. J.
影响因子：
2.8
作者：
Bryant, Adam;Moore, John
通讯作者：
Moore, John
影响因子：
16
作者：
Lobb RJ;Becker M;Wen SW;Wong CS;Wiegmans AP;Leimgruber A;Möller A
通讯作者：
Möller A
影响因子：
5.1
作者：
Marston B;Palanichamy A;Anolik JH
通讯作者：
Anolik JH
影响因子：
27.4
作者：
Nordberg, Lena Bugge;Lillegraven, Siri;Haavardsholm, Espen Andre
通讯作者：
Haavardsholm, Espen Andre