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 (NLR、PLR、SII、LMR) 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, SII) were associated with an increased risk of ALS incidence (per SD increment HR, 95% CI: 1.15, 1.02-1.29 for neutrophils; 1.15, 1.03-1.28 for NLR; and 1.17, 1.05-1.30 for SII). Subgroup and interaction analyses revealed that BMI and age had specific effects on this association. In participants with BMI≥25 or age<65, higher neutrophil counts and their metrics increased the risk of incident ALS; however, in participants with BMI<25 or age≥65, 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. This article is protected by copyright. All rights reserved.