Inflammatory profile in LRRK2-associated prodromal and clinical PD.
Inflammatory profile in LRRK2-associated prodromal and clinical PD.
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DOI：
10.1186/s12974-016-0588-5
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发表时间：
2016-05-24
影响因子：
9.3
通讯作者：
Maetzler W
中科院分区：
文献类型：
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作者：
Brockmann K;Apel A;Schulte C;Schneiderhan-Marra N;Pont-Sunyer C;Vilas D;Ruiz-Martinez J;Langkamp M;Corvol JC;Cormier F;Knorpp T;Joos TO;Gasser T;Schüle B;Aasly JO;Foroud T;Marti-Masso JF;Brice A;Tolosa E;Marras C;Berg D;Maetzler W
有证据表明炎症在帕金森病（PD）的发病机制中具有相关作用。LRRK 2基因突变是常染色体显性遗传性PD最常见的遗传原因。LRRK 2在巨噬细胞和小胶质细胞中高度表达，表明参与炎症途径。目的是测试（1）特发性PD和LRRK 2相关PD是否具有共同的炎症途径或存在不同的特征，以及（2）非表现性LRRK 2突变携带者是否存在与PD患者相似的炎症特征。我们评估了来自MJFF LRRK 2联盟的534名个体的23种免疫相关标志物和脑源性神经营养因子的血清谱。很大一部分炎症标志物具有性别依赖性。两个受PD影响的队列均显示促炎标志物脂肪酸结合蛋白水平升高。此外，特发性PD患者（而非LRRK 2相关PD患者）的促炎标志物白细胞介素-12-p40以及抗炎物质白细胞介素-10、脑源性神经营养因子和干细胞因子水平升高。未表现出LRRK 2突变的携带者，包括具有PD前驱特征的携带者，表现出对照样炎症特征。伴随炎症似乎与特发性和LRRK 2相关PD相关。确定炎症过程在其病理生理学中起主要作用的PD患者可能至少为患者亚组提供新的治疗窗口。由于具有PD前驱期症状的非表现性LRRK 2突变携带者未显示炎症特征，因此免疫系统的激活似乎不是疾病级联中的早期事件。本文的在线版本（doi：10.1186/s12974-016-0588-5）包含补充材料，可供授权用户使用。
There is evidence for a relevant role of inflammation in the pathogenesis of Parkinson’s disease (PD). Mutations in the LRRK2 gene represent the most frequent genetic cause for autosomal dominant PD. LRRK2 is highly expressed in macrophages and microglia suggesting an involvement in inflammatory pathways. The objectives are to test (1) whether idiopathic PD and LRRK2-associated PD share common inflammatory pathways or present distinct profiles and (2) whether non-manifesting LRRK2 mutation carriers present with similar aspects of inflammatory profiles as seen in PD-affected patients. We assessed serum profiles of 23 immune-associated markers and the brain-derived neurotrophic factor in 534 individuals from the MJFF LRRK2 consortium. A large proportion of inflammatory markers were gender-dependent. Both PD-affected cohorts showed increased levels of the pro-inflammatory marker fatty-acid-binding protein. Additionally, idiopathic PD but not LRRK2-associated PD patients showed increased levels of the pro-inflammatory marker interleukin-12-p40 as well as the anti-inflammatory species interleukin-10, brain-derived neurotrophic factor, and stem cell factor. Non-manifesting LRRK2 mutation carriers including those with prodromal characteristics of PD presented with control-like inflammatory profiles. Concomitant inflammation seems to be associated with idiopathic and LRRK2-associated PD. Identifying PD patients in whom inflammatory processes play a major role in their pathophysiology might offer a new therapeutic window at least for a subgroup of patients. Since non-manifesting LRRK2 mutation carriers with symptoms of the prodromal phase of PD did not show inflammatory profiles, activation of the immune system seems not an early event in the disease cascade. The online version of this article (doi:10.1186/s12974-016-0588-5) contains supplementary material, which is available to authorized users.