Peripheral lymphocyte subsets in spinocerebellar Ataxia type 2: Insights into disease mechanisms and potential...

Spinocerebellar Ataxia type 2 (SCA2), caused by CAG repeat expansions in ATXN2, involves a multifaceted molecular pathophysiology. Although immune system involvement is an emerging area of focus in SCA2 research, the profile of peripheral lymphocyte subsets remains largely unexplored.

This study was aimed to determine the percentage of specific lymphocyte subpopulations in SCA2 patients and assessing their association with key demographic and clinical features, the CAG repeats and inflammatory markers.

Peripheral blood mononuclear cells from 31 SCA2 patients and 23 age-and gender matched healthy controls were analyzed by flow cytometry to determine the proportions of up to nine lymphocyte subpopulations. Clinical assessments included ataxia severity, non-ataxia symptoms, cognitive dysfunction, and inflammatory markers derived from blood cell counts.

Analysis of lymphocyte subpopulations revealed a significant increase in CD20⁺ B lymphocytes and HLA-DR⁺ cells in SCA2 patients compared with controls. Although only nominally significant, the CD4/CD8 ratio and the proportion of activated CD20⁺HLA-DR⁺ B cells were reduced in patients, accompanied by increases in overall CD25⁺ and CD126⁺ lymphocyte populations. Platelet counts were significantly associated with helper T-cell measures, whereas specific lymphocyte subsets showed nominal correlations with gender, CAG repeats, ataxia severity and cognitive performance.

This study highlights subtle immune alterations in SCA2, especially in lymphocyte profiles, reflecting complex immune dysregulation. These findings provide new insights into the role of adaptative immune mechanisms in SCA2 pathogenesis and underscore the importance of further comprehensive immune profiling to advance understanding and therapeutic development.