Elevated Serum MCP‐2 and TARC Associated With Increased Risk of Death in Guamanian ALS Patients

TL;DR

High levels of two immune proteins in Guamanian ALS patients are linked to shorter survival times, suggesting a role in disease progression.

Contribution

Identifies MCP-2 and TARC as novel serum biomarkers associated with increased mortality risk in Guamanian ALS patients.

Findings

Elevated MCP-2 and TARC levels correlate with a 38% higher risk of death in Guamanian ALS patients.

Factor analysis revealed two key cytokine patterns explaining 68% of the variation in immune markers.

Inflammation is linked to shorter lifespan in this unique ALS population.

Abstract

This study explores the relationship between inflammation and longevity in a high‐incidence focus of amyotrophic lateral sclerosis (ALS) in post‐WWII Guam. Characteristics of this focus include the sudden appearance of the disease in high numbers and the unusually long lifespan (without medical interventions) seen in some cases. We used bio‐banked specimens to evaluate the relationship between serum immunoregulators and survival time.

We evaluated sera from 69 Guam ALS cases collected within 2 years of symptom onset by NIH researchers from 1950 to 1983 for 11 immunoregulators via ELISA (CRP, eotaxin‐1, RANTES, IL‐6, IL‐8, IL‐10, IFN‐γ, IP‐10, MCP‐1, MCP‐2 and TARC). Factor analysis identified two factors responsible for ~68% of the variation in the data. We estimated Cox proportional hazards models to identify immunoregulators associated with time to death.

Each 10‐unit increase in factor 2 cytokines (MCP‐2 and TARC) was associated with a 38% increase in the risk of death (HR: 1.38; 95% CI: 1.19, 1.65; p: 0.00). Discussion: Like sporadic ALS cases worldwide, inflammation is associated with a shortened lifespan in Guamanian ALS; more specifically, our findings suggest serum levels of MCP‐2 and TARC at onset may predict disease duration. Further investigation is needed to determine the role of these immunoregulators in disease prognosis and as targets for diagnostic and therapeutic interventions.

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