Neutrophils Are Associated with Higher Risk of Incident Amyotrophic Lateral Sclerosis in a BMI- and Age-Dependent Manner

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology Pub Date : 2023-08-09 DOI:10.1002/ana.26760

Wen Cao PhD, Zhi Cao PhD, Yao Tian MS, Linjing Zhang PhD, Wenjing Wang PhD, Lu Tang PhD, Chenjie Xu PhD, Dongsheng Fan MD, PhD

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引用次数: 1

Abstract

Objective

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.

Methods

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.

Results

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.

Interpretation

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

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中性粒细胞与肌萎缩侧索硬化症的高发病风险相关，这取决于BMI和年龄。

目的：外周免疫标志物与肌萎缩侧索硬化症（ALS）的进展和预后有关。然而，外周免疫失调是ALS的危险因素还是运动神经元变性的结果尚未明确。我们旨在确定未知前外周免疫与ALS发病风险之间的纵向关联。方法：2006年至2010年间，英国生物库共有345000名个体被纳入基线。通过Cox比例风险模型分析了外周免疫标志物（中性粒细胞、淋巴细胞、单核细胞、血小板和CRP）的计数及其衍生指标（中性粒细胞核与淋巴细胞比率[NLR]、血小板与淋巴细胞比率[PLR]、淋巴细胞与单核细胞比率[LMR]和全身免疫炎症指数[SII]）与以下ALS事件的关系。进行了亚组和交互作用分析，以进一步探索这些关系的协变量。结果：在调整了所有协变量后，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发病率的增加有关（每SD增量危险比[HR] = 1.15，95%置信区间[CI] = 中性粒细胞1.02-1.29；小时 = 1.15，95%CI = NLR为1.03-1.28；和人力资源 = 1.17，95%CI = 对于SII为1.05-1.30）。亚组和相互作用分析显示，体重指数（BMI）和年龄对这种关联有特定的影响。在BMI≥ 25岁或年龄解释：我们的研究提供了证据，证明中性粒细胞水平和中性粒细胞衍生指标（NLR和SII）的增加与ALS发病风险的增加有关。神经网络2023；94:942-954。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.