Mitchell R M, Freeman W M, Randazzo W T, Stephens H E, Beard J L, Simmons Z, Connor J R
Department of Neurosurgery, Pennsylvania State University College of Medicine/Milton S. Hershey Medical Center, Hershey, PA 17033-0850, USA.
Neurology. 2009 Jan 6;72(1):14-9. doi: 10.1212/01.wnl.0000333251.36681.a5. Epub 2008 Nov 5.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with complicated pathogenesis that poses challenges with respect to diagnosis and monitoring of disease progression.
To identify a biomarker panel that elucidates ALS disease pathogenesis, distinguishes patients with ALS from neurologic disease controls, and correlates with ALS disease characteristics, and to determine the effect of HFE gene variants, a potential risk factor for sporadic ALS, on the biomarker profile.
We obtained CSF samples by lumbar puncture from 41 patients with ALS and 33 neurologic disease controls. All patients were genotyped for HFE polymorphisms. We performed a multiplex cytokine and growth factor analysis and immunoassays for iron-related analytes. Classification statistics were generated using a support vector machine algorithm.
The groups of patients with ALS and neurologic disease controls were each associated with distinct profiles of biomarkers. Fourteen biomarkers differed between patients with ALS and the control group. The five proteins with the lowest p values differentiated patients with ALS from controls with 89.2% accuracy, 87.5% sensitivity, and 91.2% specificity. Expression of IL-8 was higher in those patients with lower levels of physical function. Expression of beta2-microglobulin was higher in subjects carrying an H63D HFE allele, while expression of several markers was higher in subjects carrying a C282Y HFE allele.
A CSF inflammatory profile associated with amyotrophic lateral sclerosis (ALS) pathogenesis may distinguish patients with ALS from neurologic disease controls, and may serve as a biomarker panel to aid in the diagnosis of ALS pending further validation. Some of these biomarkers differ by HFE genotype.
肌萎缩侧索硬化症（ALS）是一种发病机制复杂的进行性神经退行性疾病，在疾病诊断和进展监测方面存在挑战。
确定一个生物标志物组合，以阐明ALS疾病发病机制，将ALS患者与神经疾病对照区分开来，并与ALS疾病特征相关联，同时确定HFE基因变异（散发性ALS的一个潜在危险因素）对生物标志物谱的影响。
我们通过腰椎穿刺从41例ALS患者和33例神经疾病对照中获取脑脊液样本。对所有患者进行HFE多态性基因分型。我们进行了多重细胞因子和生长因子分析以及铁相关分析物的免疫测定。使用支持向量机算法生成分类统计数据。
ALS患者组和神经疾病对照组各自具有独特的生物标志物谱。ALS患者和对照组之间有14种生物标志物存在差异。p值最低的5种蛋白质区分ALS患者和对照组的准确率为89.2%，灵敏度为87.5%，特异性为91.2%。身体功能水平较低的患者中IL-8表达较高。携带H63D HFE等位基因的受试者中β2-微球蛋白表达较高，而携带C282Y HFE等位基因的受试者中几种标志物的表达较高。
与肌萎缩侧索硬化症（ALS）发病机制相关的脑脊液炎症谱可能将ALS患者与神经疾病对照区分开来，并可作为一个生物标志物组合，在进一步验证之前辅助ALS的诊断。其中一些生物标志物因HFE基因型而异。
