Abstract Details

Title Deep Immunophenotyping Reveals ‘Older’ T cell And B cell Compartments in Patients with Parkinson’s Disease

Topic Movement Disorders

Presentation(s) S10 - Biomarkers in Movement Disorders (3:52 PM-4:03 PM)

Poster/Presentation
Number 003

Background Accumulating evidence suggests that the immune system may play an important role in the pathogenesis of Parkinson’s disease (PD). In particular. abnormal T cell responses have been described in patients with PD.

Objective

The aim of the current study was to comprehensively immunophenotype the peripheral immune compartment in the patients with PD.

Design/Methods This is a cross-sectional study. Venous blood was collected from patients with PD (n=15) as well as age- and sex-matched controls (n=17). Multi-parametric (16 colors) flow cytometry was performed blindly on both fresh whole blood leukocytes or Ficoll-gradient isolated and cryopreserved peripheral blood mononuclear cells (PBMC). Comprehensive immune-cell subset phenotypic and functional-response profiling was carried out, under both resting and activated conditions. FlowJo and Cytobank were used to analyze the FACS data. Hierarchical clustering by Spearman rank correlation was used to unbiasedly segregate groups based on the flow staining pattern.

Results The average frequency of circulating CD4⁺ T cells was decreased (p=0.008), while CD8⁺ T cell frequency increased (p=0.0015), in the PD patients relative to controls, resulting in a 40% decrease of their CD4/CD8 ratios (p=0.002). PD patients notably harbored higher number of more immunosenescent (CD28^- CD27^- CD57⁺ KLRG1⁺) T cells (p=0.05). Similarly, the frequency of age-associated CD11c⁺B cells was increased (p=0.009), while newly generated transitional B cells with immune-regulatory capacity were decreased, in the PD group (p=0.0072).

Conclusions Taken together, our data points to accelerated aging of distinct immune cells subsets within both the T cell and B cell compartments in patients with PD. These alterations may provide an explanation for the pro-inflammatory immune-profile described in PD patients. Further functional and mechanistic study is warranted.

Authors/Disclosures
Rui Li (McGill University) PRESENTER	No disclosure on file
	No disclosure on file
Maria E. Diaz Ortiz, MD, PhD (Columbia Neurology)	No disclosure on file
Roy Alcalay, MD (Columbia University)	Dr. Alcalay has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genzyme/Sanofi. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gain Therapeutics. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vanqua Bio. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Capsida. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Servier. The institution of Dr. Alcalay has received research support from Michael J. Fox Foundation. The institution of Dr. Alcalay has received research support from Parkinson's Foundation. The institution of Dr. Alcalay has received research support from Silverstein Foundation. Dr. Alcalay has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant with Parkinson's Foundation.
Thomas F. Tropea, DO (University of Pennsylvania)	Dr. Tropea has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bial. The institution of Dr. Tropea has received research support from NINDS. The institution of Dr. Tropea has received research support from Parkinson Foundation. The institution of Dr. Tropea has received research support from Michael J Fox Foundation.
Alice Chen-Plotkin, MD	Dr. Chen-Plotkin has received intellectual property interests from a discovery or technology relating to health care.
Amit Bar-Or, MD, FRCPC (University of Pennsylvania)	Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merk/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for cabaletta. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. The institution of Dr. Bar-Or has received research support from Novartis. The institution of Dr. Bar-Or has received research support from Biogen. The institution of Dr. Bar-Or has received research support from Roche/Genentech.

��ɫ��

��ɫ��