In 40 PD patients, regulatory NK cells (CD56+CD16-) showed a significant, disease-duration-dependent decline in CD56 expression (lower MFI) without changes in subset proportions or correlations with UPDRS or dopaminergic dose.

This provides a peripheral, inflammation-related biomarker candidate reflecting impaired immunoregulatory capacity in advanced PD that could help stage disease or stratify patients for immune-modulatory approaches, albeit requiring validation and mechanistic follow-up.

INTRODUCTION: Neuroinflammation and peripheral immune dysregulation play critical roles in the pathophysiology of Parkinson's disease (PD); however, the clinical significance of natural killer (NK) cells remains incompletely understood. This study aimed to characterize the immunophenotypic profile of peripheral NK cells in patients with PD and to explore their association with disease duration and clinical manifestations. METHODS: Forty patients with PD were enrolled and stratified by median disease duration into ≤10 years and ≥11 years groups. Peripheral blood mononuclear cells were analyzed by flow cytometry to identify NK cells (CD3-CD56+) and their subsets, including regulatory (CD56+CD16-) and cytotoxic (CD56+CD16+) NK cells. Mean fluorescence intensity (MFI) of CD56 and CD16 was quantified. Associations between NK cell indices and clinical variables were evaluated. RESULTS: While the proportions of NK cell subsets did not differ significantly between groups, the CD56 MFI of regulatory NK cells was significantly lower in patients with longer disease duration (31.80 ± 8.88 vs. 45.84 ± 16.90; p = 0.006). Disease duration was negatively correlated with CD56 MFI of regulatory NK cells (r = -0.394, p = 0.012), which remained significant after adjustment for age, sex, and body mass index. No significant correlations were observed between NK cell parameters and the MDS-UPDRS scores or levodopa-equivalent daily dose. CONCLUSIONS: Regulatory NK cells exhibit a progressive reduction in CD56 expression with longer disease duration in PD, suggesting impaired immunoregulatory capacity in advanced disease stages. These phenotypic alterations may serve as peripheral markers of disease chronicity and immune dysfunction.