Objective: We aimed to compare peripheral blood mononuclear cell (PBMC) subsets between Parkinson’s disease (PD) and multiple system atrophy (MSA) to identify disease-specific immune signatures and their correlations with disease severity.

Background: Both PD and MSA are neurodegenerative disorders characterized by abnormal alpha-synuclein aggregation. Dysregulated immune responses may contribute to neuronal damage and the accumulation of alpha-synuclein. The distinct pathogenic mechanisms of PD and MSA may be influenced by differences in immune response.

Method: PBMC subsets were analyzed by flow cytometry in 69 PD patients, 38 MSA patients, and 69 healthy controls (HC). Age-adjusted ANCOVA, Tukey’s post-hoc test, and pathway analyses were performed.

Results: MSA patients showed significantly higher CD4+ T cells (p<0.001), regulatory T cells (p=0.002), and Th2 cells (p=0.013) compared to PD and HC. FOXP3 expression in regulatory T cells was also significantly elevated in MSA (p=0.001) compared to PD and HC. Patients with PD exhibited increased cDC2 cells (p=0.015) and intermediate monocytes (p=0.031). In PD, higher Hoehn & Yahr scores correlated with increased CD4+ TEM (p=0.018), Th1 (p=0.027), and CD8+ TEMRA cells (p=0.014). In patients with MSA, disease severity correlated with increased naive B cells (p=0.021) and transitional B cells (p=0.033), suggesting a shift towards regulatory and anti-inflammatory immune responses.

Conclusion: PD and MSA patients display distinct immune signatures in PBMC, with pro-inflammatory responses in PD and regulatory/anti-inflammatory shifts in MSA. These immune alterations correlate with disease severity, providing insight into disease-specific immune mechanisms.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/distinct-peripheral-immune-profiles-of-parkinsons-disease-and-multiple-system-atrophy/