Immunomodulatory effect and clinical outcome in Parkinson's disease patients on levodopa-pramipexole combo therapy: A two-year prospective study
Immunomodulatory effect and clinical outcome in Parkinson's disease patients on levodopa-pramipexole combo therapy: A two-year prospective study
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DOI：
10.1016/j.jneuroim.2020.577328
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发表时间：
2020-10-15
影响因子：
3.3
通讯作者：
Adalid-Peralta, Laura
中科院分区：
文献类型：
--
作者：
Espinosa-Cardenas, Raquel;Arce-Sillas, Asiel;Adalid-Peralta, Laura
帕金森病(PD)是第二常见的神经退行性疾病，已被认为与中枢和外周炎症增加有关。虽然免疫系统对多巴胺能治疗的反应仍不完全清楚，但已知的是，多巴胺能激动剂具有免疫调节特性，这可能至少部分解释了它们对帕金森病的治疗效果。这突出了在接受特定治疗方案的PD患者的纵向研究中分析免疫参数的必要性。在这项工作中，帕金森病患者参加了一项为期两年的前瞻性研究，比较了左旋多巴单独治疗和左旋多巴/普拉克索联合治疗对几种调节性和促炎免疫细胞群的影响。我们证明，通过流式细胞仪检测，帕金森病患者的循环中几个重要的调节亚群的水平降低。值得注意的是，当左旋多巴单独使用时，可降低功能性Bregs和SLAMF1+耐受树突状细胞的水平，增加总单核细胞和人类白细胞抗原DR+经典单核细胞的水平，而普拉克索/左旋多巴联合应用可促进Treg和耐受树突状细胞介导的调节反应。这些结果表明，仅以左旋多巴为基础的方案可能会促进PD患者的促炎型反应，但当与普拉克索联合使用时，它会促进临床有益的调节型环境。
Parkinson's disease (PD), the second most frequent neurodegenerative disease, has been linked to increased central and peripheral inflammation. Although the response of the immune system to dopaminergic treatment remains to be fully understood, dopaminergic agonists are known to exhibit immunoregulatory properties which may, at least in part, explain their therapeutic effect in PD. This highlights the need of analyzing immune parameters in longitudinal studies on PD patients receiving specific therapeutic regimes. In this work, PD patients were included in a two-year prospective study comparing the effect of levodopa alone and a levodopa/pramipexole combo therapy on several regulatory and pro-inflammatory immune cell populations. We demonstrated that PD patients show decreased circulating levels of several important regulatory subpopulations, as determined by flow cytometry. Notably, when administered alone, levodopa decreased the levels of functional Bregs and SLAMF1+ tolerogenic DCs and increased the levels of total and HLA-DR+ classical monocytes, while the pramipexole/levodopa combo may promote Treg- and tolerogenic DC-mediated regulatory responses. These results suggest that a regime based on levodopa alone may promote a pro-inflammatory-type response in PD patients, but when combined with pramipexole, it promotes a clinically beneficial regulatory-type environment.