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帕金森病外周免疫生物标志物特征:一项多中心、横断面和纵向研究。

Parkinson's disease peripheral immune biomarker profile: a multicentre, cross-sectional and longitudinal study.

机构信息

Department of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.

Department of Neurology, The Affiliated Hospital of Jining Medical University, Jining, 272000, China.

出版信息

J Neuroinflammation. 2022 May 24;19(1):116. doi: 10.1186/s12974-022-02481-3.

Abstract

BACKGROUND

Inflammations play crucial role in the pathogenesis of Parkinson's disease (PD), however, their possible value in the diagnosis or tracking of the progress of PD is still limited, because of discordant results in the literature and a lack of information regarding its reproducibility. Thus, overall longitudinal and cross-sectional studies are needed. This multicentre study was designed to investigate the association between multiple peripheral immune biomarkers and the development and progression of PD.

METHODS

This was a longitudinal and multicentre study. First, we measured the levels of five typical cytokines and five focused chemokines in 76 PD patients and 76 healthy controls (HCs) in a discovery cohort. Then, a validation cohort of 80 PD and 80 HC participants was recruited from four multicentre locations. In addition, a prospective follow-up of early-stage PD patients was performed with significant biomarkers. Finally, we performed further verification in an exploratory set of patients with idiopathic REM sleep behaviour disorder (iRBD).

RESULTS

In the discovery set, CXCL12, CX3CL1 and IL-8 levels were significantly higher in PD patients than in HCs (p < 0.05). The receiver-operating characteristic (ROC) curve for a combination of these three biomarkers produced a high area under the curve (AUC) of 0.89 (p < 0.001). Moreover, four biomarkers (the previous three and CCL15) were significantly associated with PD in the discovery and validation cohorts. Furthermore, in the prospective follow-up cohort, CX3CL1 levels were associated with motor progression after a mean interval of 43 months. In addition, CX3CL1 and IL-8 levels were higher in iRBD patients than in HCs.

CONCLUSION

We showed a correlation between a profile of four peripheral immune biomarkers and PD development and progression. Our findings may provide a basis whereby PD patients with abnormal inflammatory profiles can be identified and receive timely therapeutic interventions.

摘要

背景

炎症在帕金森病(PD)的发病机制中起着至关重要的作用,然而,由于文献中结果不一致,以及缺乏关于其可重复性的信息,其在 PD 的诊断或进展跟踪中的可能价值仍然有限。因此,需要进行全面的纵向和横断面研究。本多中心研究旨在探讨多种外周免疫生物标志物与 PD 的发生和发展的关系。

方法

这是一项纵向和多中心研究。首先,我们在发现队列中测量了 76 名 PD 患者和 76 名健康对照者(HCs)的五种典型细胞因子和五种聚焦趋化因子的水平。然后,从四个多中心地点招募了 80 名 PD 和 80 名 HCs 参加验证队列。此外,对有早期 PD 患者进行了具有显著生物标志物的前瞻性随访。最后,我们在一组特发性 REM 睡眠行为障碍(iRBD)患者中进行了进一步验证。

结果

在发现组中,CXCL12、CX3CL1 和 IL-8 水平在 PD 患者中明显高于 HCs(p<0.05)。这三种生物标志物组合的受试者工作特征(ROC)曲线产生了 0.89 的高曲线下面积(AUC,p<0.001)。此外,在发现和验证队列中,有四个生物标志物(前三个和 CCL15)与 PD 显著相关。此外,在前瞻性随访队列中,CX3CL1 水平与平均间隔 43 个月后的运动进展相关。此外,iRBD 患者的 CX3CL1 和 IL-8 水平高于 HCs。

结论

我们显示了四种外周免疫生物标志物与 PD 发生和进展之间的相关性。我们的发现可能为识别具有异常炎症谱的 PD 患者并及时进行治疗干预提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01ae/9131564/dec615d7a008/12974_2022_2481_Fig1_HTML.jpg

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