Brockmann K, Schulte C, Schneiderhan-Marra N, Apel A, Pont-Sunyer C, Vilas D, Ruiz-Martinez J, Langkamp M, Corvol J-C, Cormier F, Knorpp T, Joos T O, Bernard A, Gasser T, Marras C, Schüle B, Aasly J O, Foroud T, Marti-Masso J F, Brice A, Tolosa E, Berg D, Maetzler W
Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Eur J Neurol. 2017 Feb;24(2):427-e6. doi: 10.1111/ene.13223.
The presentation of Parkinson's disease patients with mutations in the LRRK2 gene (PD ) is highly variable, suggesting a strong influence of modifying factors. In this context, inflammation is a potential candidate inducing clinical subtypes.
An extensive battery of peripheral inflammatory markers was measured in human serum in a multicentre cohort of 142 PD patients from the MJFF LRRK2 Consortium, stratified by three different subtypes as recently proposed for idiopathic Parkinson's disease: diffuse/malignant, intermediate and mainly pure motor.
Patients classified as diffuse/malignant presented with the highest levels of the pro-inflammatory proteins interleukin 8 (IL-8), monocyte chemotactic protein 1 (MCP-1) and macrophage inflammatory protein 1-β (MIP-1-β) paralleled by high levels of the neurotrophic protein brain-derived neurotrophic factor (BDNF). It was also possible to distinguish the clinical subtypes based on their inflammatory profile by using discriminant and area under the receiver operating characteristic curve analysis.
Inflammation seems to be associated with the presence of a specific clinical subtype in PD that is characterized by a broad and more severely affected spectrum of motor and non-motor symptoms. The pro-inflammatory metabolites IL-8, MCP-1 and MIP-1-β as well as BDNF are interesting candidates to be included in biomarker panels that aim to differentiate subtypes in PD and predict progression.
携带富亮氨酸重复激酶2基因（LRRK2）突变的帕金森病（PD）患者的临床表现高度可变，提示修饰因素有强大影响。在此背景下，炎症是诱导临床亚型的潜在因素。
在来自迈克尔·J·福克斯基金会LRRK2联盟的142例PD患者的多中心队列中，检测人血清中一系列广泛的外周炎症标志物，并根据最近针对特发性帕金森病提出的三种不同亚型进行分层：弥漫性/恶性型、中间型和主要为纯运动型。
分类为弥漫性/恶性型的患者，促炎蛋白白细胞介素8（IL-8）、单核细胞趋化蛋白1（MCP-1）和巨噬细胞炎性蛋白1-β（MIP-1-β）水平最高，同时神经营养蛋白脑源性神经营养因子（BDNF）水平也高。通过判别分析和受试者工作特征曲线下面积分析，也能够根据炎症特征区分临床亚型。
炎症似乎与PD中一种特定临床亚型的存在相关，该亚型的特征是运动和非运动症状的范围更广且受影响更严重。促炎代谢产物IL-8、MCP-1和MIP-1-β以及BDNF是有望纳入旨在区分PD亚型和预测疾病进展的生物标志物组合中的有趣候选物。
