ArticleAnnals of clinical and translational neurology2023
The role of peripheral immunity in ALS: a population-based study.
Article in Annals of clinical and translational neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 23 citations in OpenAlex.
- Respiratory Function Improvement and Lifespan Extension Following Immunotherapy with NP001 Support the Concept That Amyotrophic Lateral Sclerosis (ALS) Is an Immuno-Neurologic Disease.International journal of molecular sciences · 2025Trial
- Sex-associated differences in routine inflammatory markers and neuromuscular ultrasound measurements in amyotrophic lateral sclerosis: a retrospective cross-sectional study.Annals of medicine · 2026Article
- Review
- A Blood-Derived Factor Rescues ALS: Platelet Factor 4 Activates OPTN-Dependent Autophagy to Clear SOD1 Aggregates Independently of PINK1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The role of the peripheral immune system in mediating axonal dysfunction in early-stage amyotrophic lateral sclerosis: An age- and sex-based analysis.Neural regeneration research · 2026Article
- Sex-Specific Genetic Architecture of ALS: Evidence of a Female Protective Effect?Annals of neurology · 2026Article
- Peripheral Neutrophil Activation and Extracellular Trap Formation in Amyotrophic Lateral Sclerosis.Annals of clinical and translational neurology · 2026Article
- Before Symptoms Begin: Immune Activation in Preclinical ALS.Annals of neurology · 2026Article
- Neutrophil-to-lymphocyte ratio in amyotrophic lateral sclerosis: a systematic review and meta-analysis.Brain communications · 2026Review
- Tracing neuroinflammation in neurodegeneration: insights from a scoping review on biofluid biomarkers.Brain communications · 2026Review
- Spatiotemporal Dynamics and Cellular States of Neuroinflammation in Amyotrophic Lateral Sclerosis: Implications for Stage‑Specific Therapeutics.ASN neuro · 2026Review
- White Blood Cells in Neurodegenerative Diseases in the Context of Neuroinflammation.Molecular neurobiology · 2025Review
- Predicting Amyotrophic Lateral Sclerosis Mortality With Machine Learning in Diverse Patient Databases.Muscle & nerve · 2025Article
- Neutrophil-to-Lymphocyte Ratio in the Alzheimer's Disease Continuum.International journal of molecular sciences · 2025Review
- Whole-genome bisulfite sequencing of cell-free DNA unveils age-dependent and ALS-associated methylation alterations.Cell & bioscience · 2025Article
- Associations between vitamin K and systemic immune and inflammation biomarkers: a population-based study from the NHANES (2007-2020).Frontiers in nutrition · 2025Article
- The systemic inflammation markers as potential predictors of disease progression and survival time in amyotrophic lateral sclerosis.Frontiers in neuroscience · 2025Article
- Prognostic Value of Systemic Inflammation, Nutritional Status and Sarcopenia in Patients With Amyotrophic Lateral Sclerosis.Journal of cachexia, sarcopenia and muscle · 2024Article
- Novel Therapeutic Strategies in Alzheimer's Disease: Pitfalls and Challenges of Anti-Amyloid Therapies and Beyond.Journal of clinical medicine · 2024Review
- Tregs levels and phenotype modifications during Amyotrophic Lateral Sclerosis course.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSystemic inflammation has been proposed as a relevant mechanism in amyotrophic lateral sclerosis (ALS). Still, comprehensive data on ALS patients' innate and adaptive immune responses and their effect on the clinical phenotype are lacking. Here, we investigate systemic immunity in a population-based ALS cohort using readily available hematological indexes.
methodsWe collected clinical data and the complete blood count (CBC) at diagnosis in ALS patients from the Piemonte and Valle d'Aosta Register for ALS (PARALS) from 2007 to 2019. Leukocytes populations, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic-immune-inflammation index (SII), and lymphocyte-to-monocyte ratio (LMR) were derived from CBC. All variables were analyzed for association with clinical features in the entire cohort and then in sex- and age-based subgroups.
resultsNeutrophils (P = 0.001) and markers of increased innate immunity (NLR, P = 0.008 and SII, P = 0.006) were associated with a faster disease progression. Similarly, elevated innate immunity correlated with worse pulmonary function and shorter survival. The prognosis in women also correlated with low lymphocytes (P = 0.045) and a decreased LMR (P = 0.013). ALS patients with cognitive impairment exhibited lower monocytes (P = 0.0415). CONCLUSIONS AND RELEVANCE: The dysregulation of the systemic immune system plays a multifaceted role in ALS. More specifically, an elevated innate immune response is associated with faster progression and reduced survival. Conversely, ALS patients with cognitive impairment showed a reduction in monocyte count. Additionally, immune response varied according to sex and age, thus suggesting that involved immune pathways are patient specific. Further studies will help translate those findings into clinical practice or targeted treatments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.