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
{"title":"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。","authors":"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","doi":"10.1002/ana.26760","DOIUrl":null,"url":null,"abstract":"<div>\n \n <section>\n \n <h3> Objective</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Interpretation</h3>\n \n <p>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</p>\n </section>\n </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"94 5","pages":"942-954"},"PeriodicalIF":8.1000,"publicationDate":"2023-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Neutrophils Are Associated with Higher Risk of Incident Amyotrophic Lateral Sclerosis in a BMI- and Age-Dependent Manner\",\"authors\":\"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\",\"doi\":\"10.1002/ana.26760\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Interpretation</h3>\\n \\n <p>Our study provides evidence that increased neutrophil levels and neutrophil-derived metrics (NLR and SII) are associated with an increased risk of developing ALS. 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Neutrophils Are Associated with Higher Risk of Incident Amyotrophic Lateral Sclerosis in a BMI- and Age-Dependent Manner
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
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.
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