This grant builds upon the research from a prior grant: Cytokine Production by Adaptive Immune Cells in Parkinson’s Disease: Response to Diverse Biological Stimuli
Study Rationale: Studies demonstrate a role for the adaptive immune system (T-cells and B-cells) in PD. The rationale for this study is that by using enriched T-cells and B-cells and exposing the cells to biologically-relevant stimuli, we will determine if there are immunological abnormalities in these immune cell types that may influence subsequent neuroinflammatory and neurodegenerative processes. We are confident of obtaining definitive results that will advance our understanding of stimulation-dependent cytokine production and activation status by immune cells in patients with PD.
Hypothesis: We hypothesize that patients with PD have T-cell and B-cell subsets in their peripheral blood that spontaneously express pro-inflammatory cytokines and activation markers, and/or are more sensitive to stimulation to produce these disease-provoking mediators.
Study Design: The PD patient population consists of two groups: early-stage idiopathic PD (less than 2 years since clinical diagnosis; n=50) and mid-stage idiopathic PD (diagnosed more than 2 years but less than 10 years; n=50) and 100 healthy controls (HC). PD patients will have blood drawn at baseline and 12 months later. Peripheral blood mononuclear cells will be purified from whole blood, and the capability of enriched CD4+ T-cells, CD8+ T-cells and CD19+ B-cells from PD patients and HC to secrete cytokines and express activation markers in response to biologically-relevant stimuli will be assessed by several techniques. Importantly, the longitudinal design of this study will allow for correlative analysis with clinical data.
Impact on Diagnosis/Treatment of Parkinson’s disease: With the parameters employed in this application, including use of enriched populations of critical adaptive immune cells, use of cell-type and PD-specific stimuli, state-of-the-art techniques, and inclusion of 2 cohorts of PD patients with longitudinal follow-up, we are confident of obtaining definitive results on the immunological capacity of T-cells and B-cells in patients with PD. These findings will determine if abnormalities in cytokine production and/or activation markers can be used as a biomarker for PD progression.
Next Steps for Development: We will need to replicate the findings in a separate cohort of PD patients, preferably from another institution, and confirm abnormalities by adaptive immune cells. We will explore how to dampen pro-inflammatory responses and promote anti-inflammatory responses in these cells.