Expression of Transcription Factors in CD4 + T Cells as Potential Biomarkers of Motor Complications in Parkinson's Disease.

Expression of Transcription Factors in CD4 + T Cells as Potential Biomarkers of Motor Complications in Parkinson's Disease.
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DOI:
10.3233/jpd-202417
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发表时间:
2021
期刊:
Journal of Parkinson's disease
影响因子:
--
通讯作者:
Comi C
Comi C
中科院分区:
其他
文献类型:
--
作者:
Contaldi E;Magistrelli L;Milner AV;Cosentino M;Marino F;Comi C

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运动并发症(MC)的管理是帕金森病(PD)患者长期治疗的主要挑战。在这种情况下,外周适应性免疫的作用可能会提供新的见解,因为神经炎症机制已被证明是至关重要的疾病。本研究的目的是分析参与CD 4 + T细胞发育的转录因子基因,以揭示有(PMC)和无(WMC)运动并发症患者的特异性分子特征。  检测40例PD患者外周血CD 4 +T淋巴细胞转录因子TBX 21、STAT 1、STAT 3、STAT 4、STAT 6、RORC、GATA 3、FOXP 3和NR 4A 2的mRNA水平。 此外,还招募了40名年龄和性别匹配的健康对照。WMC患者具有较高水平的STAT 1和NR 4A 2(p = 0.004; p = 0.003),而在PMC中,我们发现较高水平的STAT 6(p = 0.04)。      此外,ROC曲线分析证实STAT 1和NR 4A 2是区分WMC的可行生物标志物(AUC = 0.76,95%CI 0.59-0.92,p = 0.005; AUC = 0.75,95%CI 0.58-0.90,p = 0.007)。        类似地,STAT 6检测PMC患者(AUC = 0.69,95%CI 0.52-0.86,p = 0.037)。    这些结果提供了证据表明,不同的分子标记在PD患者的CD 4+T细胞与MC和没有,从而表明他们的潜力作为MC发展的生物标志物。 
Management of motor complications (MC) represents a major challenge in the long-term treatment of Parkinson’s disease (PD) patients. In this context, the role of peripheral adaptive immunity may provide new insights, since neuroinflammatory mechanisms have been proved crucial in the disease. The aim of this study was to analyze the transcription factors genes involved in CD4 + T cells development to uncover specific molecular signatures in patients with (PMC) and without (WMC) motor complications. mRNA levels of CD4 + T lymphocytes transcription factor genes TBX21, STAT1, STAT3, STAT4, STAT6, RORC, GATA3, FOXP3, and NR4A2 were measured from 40 PD patients, divided into two groups according to motor complications. Also, 40 age- and sex-matched healthy controls were enrolled. WMC patients had higher levels of STAT1 and NR4A2 (p = 0.004; p = 0.003), whereas in PMC we found higher levels of STAT6 (p = 0.04). Also, a ROC curve analysis confirmed STAT1 and NR4A2 as feasible biomarkers to discriminate WMC (AUC = 0.76, 95%CI 0.59–0.92, p = 0.005; AUC = 0.75, 95%CI 0.58–0.90, p = 0.007). Similarly, STAT6 detected PMC patients (AUC = 0.69, 95%CI 0.52–0.86, p = 0.037). These results provide evidence of different molecular signatures in CD 4 + T cells of PD patients with and without MC, thus suggesting their potential as biomarkers of MC development.