Abstract

Background:

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.

Objective:

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.

Methods:

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.

Results:

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).

Conclusion:

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.

中文翻译：

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CD4 + T 细胞中转录因子的表达作为帕金森病运动并发症的潜在生物标志物

摘要

背景：

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在该疾病中至关重要。

客观的：

本研究的目的是分析参与 CD4 + T 细胞发育的转录因子基因，以揭示患有 (PMC) 和不患有 (WMC) 运动并发症的患者的特定分子特征。

方法：

测量了 40 名 PD 患者的 CD4 + T 淋巴细胞转录因子基因TBX21、STAT1、STAT3、STAT4、STAT6、RORC、GATA3、FOXP3和NR4A2 的mRNA 水平，根据运动并发症分为两组。此外，还招募了 40 名年龄和性别匹配的健康对照。

结果：

WMC 患者的STAT1和NR4A2水平较高（p  = 0.004；p  = 0.003），而在 PMC 中，我们发现STAT6水平较高（p  = 0.04）。此外，ROC 曲线分析证实STAT1和NR4A2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）。同样，STAT6检测到 PMC 患者（AUC = 0.69，95%CI 0.52–0.86，p  = 0.037）。

结论：

这些结果提供了患有和不患有 MC 的 PD 患者的 CD 4 + T 细胞中不同分子特征的证据，从而表明它们作为 MC 发展的生物标志物的潜力。