Department of Neurology (B.J.M., D.E.B., S.R.K., C.F.-R., C.B., B.C.C., S.A.G., E.L.F.) and A. Alfred Taubman Medical Research Institute (E.L.F.), University of Michigan, Ann Arbor.
Neurol Neuroimmunol Neuroinflamm. 2016 Jun 1;3(4):e242. doi: 10.1212/NXI.0000000000000242. eCollection 2016 Aug.
To elucidate amyotrophic lateral sclerosis (ALS) biomarkers and potential mechanisms of disease, we measured immune cell populations in whole blood from a large cohort of patients with ALS.
Leukocytes were isolated from the blood of 44 control patients and 90 patients with ALS. The percentages and total numbers of each cell population were analyzed using flow cytometry and matched with patient ALS Functional Rating Scale-Revised (ALSFRS-R) score to correlate leukocyte metrics with disease progression.
We show a significant increase in the percentage of neutrophils and a significant decrease in the percentage of CD4 T cells and CD16(-) monocytes in the blood of patients with ALS compared to controls; however, only CD16(-) monocyte levels correlated with disease progression. We also examined the monocyte surface expression of CCRL2 and CCR3; CD16(-) monocytes displayed decreased percentages and total numbers expressing CCR3, but these numbers did not correlate with ALSFRS-R score. We found that combining multiple disease metrics yielded the most accurate predictor of disease progression: the ratio of neutrophils to CD16(-) monocytes (N:M ratio) is significantly increased in patients with ALS and better correlates with disease progression than any other single metric.
These observations implicate neutrophils and monocytes as important factors in late disease progression.
为了阐明肌萎缩侧索硬化症（ALS）的生物标志物和潜在的疾病机制，我们测量了来自大量 ALS 患者的全血中的免疫细胞群体。
从 44 名对照患者和 90 名 ALS 患者的血液中分离白细胞。使用流式细胞术分析每个细胞群体的百分比和总数，并将其与患者肌萎缩侧索硬化症功能评定量表修订版（ALSFRS-R）评分相匹配，以将白细胞指标与疾病进展相关联。
与对照组相比，我们发现 ALS 患者血液中的中性粒细胞百分比显著增加，CD4 T 细胞和 CD16（-）单核细胞百分比显著降低；然而，只有 CD16（-）单核细胞水平与疾病进展相关。我们还检查了单核细胞表面 CCRL2 和 CCR3 的表达；CD16（-）单核细胞表达 CCR3 的百分比和总数均降低，但这些数字与 ALSFRS-R 评分无关。我们发现，结合多种疾病指标可以得出最准确的疾病进展预测指标：中性粒细胞与 CD16（-）单核细胞的比值（N:M 比值）在 ALS 患者中显著增加，并且比任何其他单一指标更好地与疾病进展相关。
这些观察结果表明中性粒细胞和单核细胞是疾病晚期进展的重要因素。
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