Affiliation:
1. Department of Neurology Peking University Third Hospital Beijing China
2. School of Public Health Zhejiang University School of Medicine Hangzhou China
3. School of Public Health Hangzhou Normal University Hangzhou China
4. Beijing Key Laboratory of Biomarker and Translational Research in Neurodegenerative Disorders Beijing China
Abstract
ObjectivePeripheral 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.MethodsA 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.ResultsAfter 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.InterpretationOur 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
Funder
National Natural Science Foundation of China
Subject
Neurology (clinical),Neurology
Cited by
1 articles.
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