Elevated Interleukin-8 in Spinocerebellar Ataxia Type 2: A Distinct Peripheral Immune Signature Unrelated To Disease Severity.

Abstract

Growing experimental and clinical evidence demonstrates that immune activation influences Spinocerebellar Ataxia type 2 (SCA2) phenotype, yet the specific role of proinflammatory cytokines remains unexplored. This stuyd aims to measure peripheral proinflammatory cytokine concentrations in SCA2 patients and examine their associations with clinical, genetic, and inflammatory markers. We measured serum levels of interleukin-1α (IL-1α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) using enzyme-linked immunosorbent assay in 36 spinocerebellar ataxia type 2 patients and 36 matched controls. Clinical evaluation encompassed the Scale for Assessment and Rating of Ataxia (SARA), Inventory of Non-Ataxia Symptoms count (INAS), Cerebellar Cognitive Affective Syndrome scale (CCAS-S), along with S100β protein levels and cellular inflammatory markers. We employed univariate correlation analyses to examine relationships between cytokine levels and disease characteristics. SCA2 patients demonstrated cytokine profiles similar to healthy controls, with the exception of significantly elevated IL-8 levels. Spearman correlation analysis revealed that the monocyte-to-lymphocyte ratio (MLR) was directly associated with IL-8 concentrations. Notably, no significant associations were found between the cytokine levels and demographic characteristics, age at onset, time from ataxia onset, CAG repeat length, or clinical markers of disease severity. Our study reveals selective peripheral IL-8 elevation in SCA2, independent of disease severity. While not linked to disease severity, this immune signature warrants further research to assess its prognostic or therapeutic value through larger, longitudinal studies.