The role of peripheral immunity in ALS: a population-based study

Area of Science:

• Neurology
• Immunology
• Hematology

Background:

• Systemic inflammation is implicated in amyotrophic lateral sclerosis (ALS) pathogenesis.
• Comprehensive data on immune responses in ALS patients and their clinical impact are limited.
• Hematological indexes offer a potential tool for assessing immune status in ALS.

Purpose of the Study:

• To investigate systemic immune responses in a population-based ALS cohort.
• To correlate readily available hematological indexes with ALS clinical features and prognosis.
• To explore sex- and age-specific immune variations in ALS.

Main Methods:

• Analysis of complete blood count (CBC) data from the Piemonte and Valle d'Aosta Register for ALS (PARALS) cohort (2007-2019).
• Calculation of leukocyte populations, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic-immune-inflammation index (SII), and lymphocyte-to-monocyte ratio (LMR).
• Statistical analysis of associations between immune markers and clinical features, including disease progression, pulmonary function, survival, cognitive impairment, sex, and age.

Main Results:

• Increased neutrophils, NLR, and SII correlated with faster ALS progression.
• Elevated innate immunity markers were associated with worse pulmonary function and shorter survival.
• Low lymphocytes and decreased LMR in women, and lower monocyte counts in patients with cognitive impairment were observed.

Conclusions:

• Systemic immune dysregulation plays a significant role in ALS.
• Elevated innate immunity is linked to poorer prognosis in ALS.
• Immune responses in ALS are patient-specific, varying by sex and age, suggesting potential for personalized treatment strategies.