Muñoz-Delgado Laura, Macías-García Daniel, Periñán María Teresa, Jesús Silvia, Adarmes-Gómez Astrid D, Bonilla Toribio Marta, Buiza Rueda Dolores, Jiménez-Jaraba María Del Valle, Benítez Zamora Belén, Díaz Belloso Rafael, García-Díaz Sergio, Martín-Bórnez Miguel, Pineda Sánchez Rocío, Carrillo Fátima, Gómez-Garre Pilar, Mir Pablo
Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
NPJ Parkinsons Dis. 2023 Jan 31;9(1):12. doi: 10.1038/s41531-023-00457-5.
Peripheral inflammatory immune responses are thought to play a major role in the pathogenesis of Parkinson's disease (PD). The neutrophil-to-lymphocyte ratio (NLR), a biomarker of systemic inflammation, has been reported to be higher in patients with PD than in healthy controls (HCs). The present study was aimed at determining if the peripheral inflammatory immune response could be influenced by the genetic background of patients with PD. We included a discovery cohort with 222 patients with PD (132 sporadic PD, 44 LRRK2-associated PD (with p.G2019S and p.R1441G variants), and 46 GBA-associated PD), as well as 299 HCs. Demographic and clinical data were recorded. Leukocytes and their subpopulations, and the NLR were measured in peripheral blood. Multivariate lineal regression and post-hoc tests were applied to determine the differences among the groups. Subsequently, a replication study using the Parkinson's Progression Markers Initiative cohort was performed which included 401 patients with PD (281 sPD patients, 66 LRRK2-PD patients, 54 GBA-PD patients) and a group of 174 HCs. Patients with sporadic PD and GBA-associated PD showed a significantly lower lymphocyte count, a non-significantly higher neutrophil count and a significantly higher NLR than HCs. The peripheral inflammatory immune response of patients with LRRK2-associated PD did not differ from HCs. Our study supports the involvement of a peripheral inflammatory immune response in the pathophysiology of sPD and GBA-associated PD. However, this inflammatory response was not found in LRRK2-associated PD, probably reflecting different pathogenic inflammatory mechanisms.
外周炎性免疫反应被认为在帕金森病（PD）的发病机制中起主要作用。据报道，作为全身炎症生物标志物的中性粒细胞与淋巴细胞比值（NLR）在PD患者中高于健康对照（HCs）。本研究旨在确定外周炎性免疫反应是否会受到PD患者遗传背景的影响。我们纳入了一个发现队列，其中包括222例PD患者（132例散发性PD、44例LRRK2相关PD（携带p.G2019S和p.R1441G变体）和46例GBA相关PD）以及299例HCs。记录了人口统计学和临床数据。对外周血中的白细胞及其亚群以及NLR进行了检测。应用多变量线性回归和事后检验来确定各组之间的差异。随后，使用帕金森病进展标志物倡议队列进行了一项重复研究，该队列包括401例PD患者（281例sPD患者、66例LRRK2-PD患者、54例GBA-PD患者）和一组174例HCs。散发性PD和GBA相关PD患者的淋巴细胞计数显著低于HCs，中性粒细胞计数略高于HCs且NLR显著高于HCs。LRRK2相关PD患者的外周炎性免疫反应与HCs无差异。我们的研究支持外周炎性免疫反应参与sPD和GBA相关PD的病理生理学过程。然而，在LRRK2相关PD中未发现这种炎性反应，这可能反映了不同的致病性炎症机制。
