Antigen Presentation and Lymphocyte Response in Parkinson's Disease

The way the immune system responds to certain PD-related proteins in PD donors compared to the way it responds in persons without or fewer PD related proteins is not well studied and this study aims to analyze the autoimmune response in each group. The study involves a one time visit involving brief questionnaires and a blood draw of 30 mL (approximately 2 tablespoons) to be collected.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease

Detailed Description

The role of the immune response in Parkinson's disease (PD) is controversial. Recent studies show that neurons can present MHC-I (major histocompatibility complex - class 1) molecules and therefore may be susceptible to an attack by immune cells. The investigators anticipate that the results of this study will improve our understanding of the mechanisms of immune mediated neuronal degeneration in PD. Initial results suggest that antigens are presented by neuronal MHC-I in PD, and that this could lead to T-cell mediated neuronal death. The most obvious antigen that could be differentially expressed in PD patients and controls would be alpha-synuclein (-syn): -syn oligomers appear in all Lewy bodies and Lewy neurites and are the hallmark of PD changes in the brain. This study will offer the opportunity to further characterize the immune mediated component of PD, and to continue elucidating the biology that underlies antigen presentation and T-cell cytolytic activity.

• Study Type: Observational
• Enrollment (Actual): 95

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • University of California San Diego School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Shirley Ryan Ability Lab
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with clinically confirmed Parkinson's disease and age matched controls

Description

Inclusion Criteria:

• Moderate to advanced PD with classic motor features, and must demonstrate two of the following three: rest tremor, rigidity, or bradykinesia
• Dopaminergic medication benefit (self-reported improvement)
• Age at recruitment: 50 - 90 years
• Age at diagnosis > 47
• PD duration > 3 years
• Willingness to have genotyping and genetic studies as part of laboratory research

Exclusion Criteria:

• Atypical parkinsonism or other neurological disorders
• Recent history of cancer (past 3 years)
• Autoimmune disease (except thyroid disease)
• On chronic immune-modulatory therapy (e.g. SIT (specific immunotherapy), anti-IgE)
• Inability to provide informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
PD and Controls; 50% of the participants will be healthy controls and 50% will be patients diagnosed with Parkinson's disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of subjects with T-cell immune response	Blood samples from PD patients and controls will be processed. The presence of T cell response against the candidate antigens by patient blood-derived peripheral blood mononuclear cells (PBMC) will be assessed using an enzyme-linked immunosorbent spot (ELISPOT) assay.	Day 1-2

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Michael J. Fox Foundation for Parkinson's Research
• Investigators: Principal Investigator: Roy Alcalay, MD, Columbia University

Publications and helpful links

General Publications

• Cebrian C, Zucca FA, Mauri P, Steinbeck JA, Studer L, Scherzer CR, Kanter E, Budhu S, Mandelbaum J, Vonsattel JP, Zecca L, Loike JD, Sulzer D. MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration. Nat Commun. 2014 Apr 16;5:3633. doi: 10.1038/ncomms4633.

Helpful Links

• Michael J Fox Foundation ad for study

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): February 1, 2021
• Study Completion (Actual): February 1, 2021

Study Registration Dates

• First Submitted: October 17, 2016
• First Submitted That Met QC Criteria: October 19, 2016
• First Posted (Estimate): October 20, 2016

Study Record Updates

• Last Update Posted (Actual): February 21, 2021
• Last Update Submitted That Met QC Criteria: February 18, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Parkinson's disease; autoimmunity
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: AAAN7912

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No