Department of Neurology, Peking University Third Hospital, Beijing, China.
School of Public Health, Zhejiang University School of Medicine, Hangzhou, China.
Ann Neurol. 2023 Nov;94(5):942-954. doi: 10.1002/ana.26760. Epub 2023 Aug 28.
Peripheral immune markers have been associated with the progression and prognosis of amyotrophic lateral sclerosis (ALS). However, whether dysregulation of peripheral immunity is a risk factor for ALS or a consequence of motor neuron degeneration has not yet been clarified. We aimed to identify longitudinal associations between prediagnostic peripheral immunity and the risk of incident ALS.
A total of 345,000 individuals from the UK Biobank between 2006 and 2010 were included at the baseline. The counts of peripheral immune markers (neutrophils, lymphocytes, monocytes, platelets, and CRP) and its derived metrics (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR], and systemic immune-inflammation index [SII]) were analyzed in relation to the following incident ALS by Cox proportional hazard models. Subgroup and interaction analyses were performed to explore the covariates of these relationships further.
After adjusting for all covariates, the multivariate analysis showed that high neutrophil counts and their derived metrics (NLR and SII) were associated with an increased risk of ALS incidence (per SD increment hazard ratio [HR] = 1.15, 95% confidence interval [CI] = 1.02-1.29 for neutrophils; HR = 1.15, 95% CI = 1.03-1.28 for NLR; and HR = 1.17, 95% CI = 1.05-1.30 for SII). Subgroup and interaction analyses revealed that body mass index (BMI) and age had specific effects on this association. In participants with BMI ≥ 25 or age < 65 years, higher neutrophil counts, and their metrics increased the risk of incident ALS; however, in participants with BMI < 25 or age ≥ 65 years, neutrophils had no effect on incident ALS.
Our study provides evidence that increased neutrophil levels and neutrophil-derived metrics (NLR and SII) are associated with an increased risk of developing ALS. ANN NEUROL 2023;94:942-954.
外周免疫标志物与肌萎缩侧索硬化症（ALS）的进展和预后相关。然而，外周免疫失调是 ALS 的危险因素还是运动神经元退化的结果尚不清楚。我们旨在确定诊断前外周免疫与 ALS 发病风险之间的纵向关联。
共纳入 UK Biobank 2006 年至 2010 年期间的 345000 名个体作为基线人群。分析外周免疫标志物（中性粒细胞、淋巴细胞、单核细胞、血小板和 CRP）及其衍生指标（中性粒细胞与淋巴细胞比值 [NLR]、血小板与淋巴细胞比值 [PLR]、淋巴细胞与单核细胞比值 [LMR] 和全身免疫炎症指数 [SII]）与以下事件性 ALS 的关系采用 Cox 比例风险模型。进行亚组和交互分析，以进一步探讨这些关系的协变量。
在校正所有协变量后，多变量分析显示，高中性粒细胞计数及其衍生指标（NLR 和 SII）与 ALS 发病风险增加相关（每 SD 增加的危险比 [HR] = 1.15，95%置信区间 [CI] = 1.02-1.29 用于中性粒细胞；HR = 1.15，95% CI = 1.03-1.28 用于 NLR；HR = 1.17，95% CI = 1.05-1.30 用于 SII）。亚组和交互分析显示，体重指数（BMI）和年龄对这种关联有特定影响。在 BMI≥25 或年龄<65 岁的参与者中，较高的中性粒细胞计数及其指标增加了患事件性 ALS 的风险；然而，在 BMI<25 或年龄≥65 岁的参与者中，中性粒细胞对事件性 ALS 没有影响。
我们的研究提供了证据，表明较高的中性粒细胞水平和中性粒细胞衍生指标（NLR 和 SII）与 ALS 发病风险增加相关。ANN NEUROL 2023；94:942-954。
