Cytokine profiling of extracellular vesicles isolated from plasma in myalgic encephalomyelitis/chronic fatigue syndrome: a pilot study.
Cytokine profiling of extracellular vesicles isolated from plasma in myalgic encephalomyelitis/chronic fatigue syndrome: a pilot study.
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DOI：
10.1186/s12967-020-02560-0
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发表时间：
2020-10-12
影响因子：
7.4
通讯作者：
Hanson MR
中科院分区：
文献类型：
--
作者：
Giloteaux L;O'Neal A;Castro-Marrero J;Levine SM;Hanson MR
肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）是一种病因不明的衰弱性疾病，持续至少6个月，但通常持续多年，其特征包括疲劳、认知障碍、肌痛、运动后不适和免疫系统功能障碍。细胞因子信号传导的失调可引起许多这些症状。细胞因子存在于血浆和细胞外囊泡中，但ME/CFS中EV的研究很少。因此，我们的目的是表征从ME/CFS个体和健康对照的血浆中分离的细胞外囊泡（EV）的含量（包括循环细胞因子/趋化因子谱）。我们纳入了35名ME/CFS患者和35名年龄、性别和BMI匹配的对照组。通过使用基于聚合物的沉淀方法从血浆中富集EV，并通过纳米颗粒跟踪分析（NTA）、透射电子显微镜（TEM）和免疫印迹进行表征。使用45重免疫测定来确定来自19名患者和对照的子集的血浆和分离的EV中的细胞因子水平。分析线性回归、主成分分析和细胞因子间相关性。与对照组相比，ME/CFS个体具有显著更高水平的大小为30至130 nm的EV，但总细胞外囊泡的平均大小在组间没有差异。通过Western印迹分析证实了典型EV标志物CD 63、CD 81、TSG 101和HSP 70的富集，并且通过TEM评估的形态显示两组中均质的囊泡群体。比较病例和对照组血浆和分离EV中的细胞因子浓度无显著差异。血浆中的细胞因子-细胞因子相关性揭示了ME/CFS病例中显著更高数量的相互作用，沿着有13种主要由干扰素γ诱导蛋白10（IP-10）驱动的负相关性，而在对照血浆中，在任何细胞因子中均未发现负相关性。对照组EV的网络分析显示，细胞因子间相互作用比ME/CFS组显著2.5倍，两组均呈现独特的负相关。ME/CFS患者血浆中30-130 nm EV水平升高，细胞因子间相关性显示ME/CFS组细胞因子之间的调节关系异常，与对照组血浆和EV均不同。这些细胞因子网络的紊乱进一步证明了ME/CFS的免疫失调。
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease of unknown etiology lasting for a minimum of 6 months but usually for many years, with features including fatigue, cognitive impairment, myalgias, post-exertional malaise, and immune system dysfunction. Dysregulation of cytokine signaling could give rise to many of these symptoms. Cytokines are present in both plasma and extracellular vesicles, but little investigation of EVs in ME/CFS has been reported. Therefore, we aimed to characterize the content of extracellular vesicles (EVs) isolated from plasma (including circulating cytokine/chemokine profiling) from individuals with ME/CFS and healthy controls. We included 35 ME/CFS patients and 35 controls matched for age, sex and BMI. EVs were enriched from plasma by using a polymer-based precipitation method and characterized by Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM) and immunoblotting. A 45-plex immunoassay was used to determine cytokine levels in both plasma and isolated EVs from a subset of 19 patients and controls. Linear regression, principal component analysis and inter-cytokine correlations were analyzed. ME/CFS individuals had significantly higher levels of EVs that ranged from 30 to 130 nm in size as compared to controls, but the mean size for total extracellular vesicles did not differ between groups. The enrichment of typical EV markers CD63, CD81, TSG101 and HSP70 was confirmed by Western blot analysis and the morphology assessed by TEM showed a homogeneous population of vesicles in both groups. Comparison of cytokine concentrations in plasma and isolated EVs of cases and controls yielded no significant differences. Cytokine-cytokine correlations in plasma revealed a significant higher number of interactions in ME/CFS cases along with 13 inverse correlations that were mainly driven by the Interferon gamma-induced protein 10 (IP-10), whereas in the plasma of controls, no inverse relationships were found across any of the cytokines. Network analysis in EVs from controls showed 2.5 times more significant inter-cytokine interactions than in the ME/CFS group, and both groups presented a unique negative association. Elevated levels of 30-130 nm EVs were found in plasma from ME/CFS patients and inter-cytokine correlations revealed unusual regulatory relationships among cytokines in the ME/CFS group that were different from the control group in both plasma and EVs. These disturbances in cytokine networks are further evidence of immune dysregulation in ME/CFS.
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影响因子：
2.7
作者：
Benjamini, Yoav;Krieger, Abba M.;Yekutieli, Daniel
通讯作者：
Yekutieli, Daniel
影响因子：
6.4
作者：
Boulware, David R.;Bonham, Shulamith C.;Bohjanen, Paul R.
通讯作者：
Bohjanen, Paul R.
影响因子：
4.6
作者：
Bosch S;de Beaurepaire L;Allard M;Mosser M;Heichette C;Chrétien D;Jegou D;Bach JM
通讯作者：
Bach JM
DOI：
10.1084/jem.182.1.155
发表时间：
1995-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Angiolillo AL;Sgadari C;Taub DD;Liao F;Farber JM;Maheshwari S;Kleinman HK;Reaman GH;Tosato G
通讯作者：
Tosato G
影响因子：
5.3
作者：
Bachis, A;Colangelo, AM;Mocchetti, I
通讯作者：
Mocchetti, I