Abstract：
Epstein-Barr virus (EBV) infection is approved as the main environmental trigger of multiple sclerosis (MS). In this path, we quantified ebv-miR-BART9-3p and ebv-miR-BART15 in exosomes of cerebrospinal fluid (CSF) of untreated relapsing-remitting MS (RRMS) patients in comparison with the control group. Interestingly, patients displayed significant upregulation of ebv-miR-BART9-3p (18.4-fold) and ebv-miR-BART15 (3.1-fold) expression in CSF exosomes. Moreover, the expression levels of hsa-miR-21-5p and hsa-miR-146a-5p were found to be significantly elevated in the CSF samples obtained from the patient group compared to those obtained from the HC group. The levels of Interferon-gamma (IFN-γ), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-17 (IL-17), interleukin-23 (IL-23), transforming growth factor beta (TGF-β), and tumor necrosis factor-alpha (TNF-α) were observed to be significantly elevated in the serum and CSF exosomes of the patients. The highest increase was observed in TGF-β (8.5-fold), followed by IL-23 (3.9-fold) in CSF exosomes. These findings are in agreement with the association between EBV infection and inflammatory cytokines induction. Furthermore, the ratios of TGF-β: TNF-α and TGF-β: IFN-γ attained values of 4 to 16.4 and 1.3 to 3.6, respectively, in the CSF exosomes of the patients, in comparison to those of the control group. These findings show EBV activity in RRMS patients is different from that of healthy ones. Elevation of ebv-miR-BART9-3p, ebv-miR-BART15, and inflammatory cytokines expression in CSF exosomes in RRMS patients provides a substantial link between EBV activity and the onset of the disease, as well as the transition from EBV infection to MS.
摘要：
EB病毒（EBV）感染被批准为多发性硬化症（MS）的主要环境触发因素。在这条路上,我们对未经治疗的复发缓解型MS(RRMS)患者脑脊液(CSF)外泌体中的ebv-miR-BART9-3p和ebv-miR-BART15进行了定量,并与对照组进行了比较.有趣的是,患者在CSF外泌体中显示ebv-miR-BART9-3p(18.4倍)和ebv-miR-BART15(3.1倍)表达显著上调.此外，与HC组相比,从患者组获得的CSF样品中hsa-miR-21-5p和hsa-miR-146a-5p的表达水平显著升高.干扰素-γ（IFN-γ）的水平，白细胞介素-1β（IL-1β），白细胞介素-6（IL-6），白细胞介素-17（IL-17），白细胞介素-23（IL-23），转化生长因子β（TGF-β），和肿瘤坏死因子-α（TNF-α）在患者的血清和CSF外泌体中观察到显着升高。在TGF-β中观察到最高的增加（8.5倍），其次是CSF外泌体中的IL-23（3.9倍）。这些发现与EBV感染和炎性细胞因子诱导之间的关联一致。此外，TGF-β：TNF-α和TGF-β：IFN-γ的比值分别为4比16.4和1.3比3.6，在病人的脑脊液外泌体中，与对照组相比。这些发现表明RRMS患者的EBV活性与健康患者的EBV活性不同。ebv-miR-BART9-3p的升高，ebv-miR-BART15和RRMS患者CSF外泌体中的炎性细胞因子表达提供了EBV活性与疾病发作之间的实质性联系，以及从EBV感染到MS的过渡。
