Objective: To investigate the effect of a-Syn Preformed Fibrils (PFF) on CXCR3 expression on B-cells in Parkinson’s Disease (PD) patients at early (E-PD, diagnosed less than 2 years and on PD medications for less than 1 year) and mid (M-PD, diagnosed more than 2 years but less than 10 years) disease stages using an in vitro system.
Background: PD is characterized by the accumulation of misfolded a-Synuclein (a-Syn), which can aggregate and form Lewy bodies. Emerging evidence implicates immune system dysfunction in PD pathogenesis. The chemokine receptor CXCR3, when bound to its ligands (CXCL9, CXCL10, and CXCL11), drives the migration of immune cells to inflamed tissues. Previous studies have reported the expression of CXCR3 on B-cells in Multiple Sclerosis, suggesting a role in neuroinflammation via migration into the central nervous system and secretion of pro-inflammatory cytokines, including TNF-a and IL-6. However, the role of CXCR3+ B-cells in PD remains understudied.
Method: The cohort was comprised of 96 healthy controls (HC), 49 E-PD, and 49 M-PD. CXCR3 expression in purified B-cells isolated from peripheral blood mononuclear cells was assessed by flow cytometry after a 24-hour stimulation with a variety of stimuli, including CD40 ligand (2 mg/ml) + anti-IgM (10 mg/ml), CpG (1 mM), LPS (200 ng/ml), a-Syn monomer (1 mg/ml), PFF (100 mM) and PFF + LPS.
Results: A higher frequency of CXCR3+ B-cells (CD19+CXCR3+) was observed following PFF and PFF + LPS stimulation compared to other stimuli. E-PD exhibited a higher frequency of CXCR3+ B-cells compared to HC and M-PD after PFF and PFF + LPS stimulation. Notably, there was an increased frequency of CXCR3+ memory B-cells (CD19+CD27+CXCR3+) in E-PD compared to HC and M-PD after PFF stimulation.
Conclusion: This is the first report demonstrating that CXCR3 expression on B-cells can be activated by PFF and that E-PD patients have a higher frequency of CXCR3+ and CXCR3+ memory B-cells following PFF stimulation. These findings suggest that CXCR3+ B-cells may play a critical role in the pathogenesis of early-stage PD.
To cite this abstract in AMA style:
H. Hong, M. Dean, D. Standaert, H. Qin, E. Benveniste. Alpha-Synuclein Preformed Fibrils Increase the Frequency of CXCR3+ B-cells in Early-stage Parkinson’s Disease Patients [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/alpha-synuclein-preformed-fibrils-increase-the-frequency-of-cxcr3-b-cells-in-early-stage-parkinsons-disease-patients/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/alpha-synuclein-preformed-fibrils-increase-the-frequency-of-cxcr3-b-cells-in-early-stage-parkinsons-disease-patients/