RT Journal Article
SR Electronic
T1 Abnormal B-Cell and Tfh-Cell Profiles in Patients With Parkinson Disease
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e1125
DO 10.1212/NXI.0000000000001125
VO 9
IS 2
A1 Li, Rui
A1 Tropea, Thomas Francis
A1 Baratta, Laura Rosa
A1 Zuroff, Leah
A1 Diaz-Ortiz, Maria E.
A1 Zhang, Bo
A1 Shinoda, Koji
A1 Rezk, Ayman
A1 Alcalay, Roy N.
A1 Chen-Plotkin, Alice
A1 Bar-Or, Amit
YR 2022
UL http://nn.neurology.org/content/9/2/e1125.abstract
AB Background and Objectives There has been growing interest in potential roles of the immune system in the pathogenesis of Parkinson disease (PD). The aim of the current study was to comprehensively characterize phenotypic and functional profiles of circulating immune cells in patients with PD vs controls.Methods Peripheral blood was collected from patients with PD and age- and sex-matched neurologically normal controls (NCs) in 2 independent cohorts (discovery and validation). Comprehensive multicolor flow cytometry was performed on whole blood leukocytes and peripheral blood mononuclear cells to characterize different immune subsets and their ex vivo responses.Results The discovery cohort included 17 NCs and 12 participants with PD, and the validation cohort included 18 NCs and 18 participants with PD. Among major immune cell types, B cells appeared to be preferentially affected in PD. Proliferating B cell counts were decreased in patients with PD compared with controls. Proportions of B-cell subsets with regulatory capacity such as transitional B cells were preferentially reduced in the patients with PD, whereas proportions of proinflammatory cytokine-producing B cells increased, resulting in a proinflammatory shift of their B-cell functional cytokine responses. Unsupervised principal component analysis revealed increased expression of TNFα and GM-CSF by both B cells and T cells of patients with PD. In addition, levels of follicular T cells, an important B-cell helper T-cell population, decreased in the patients with PD, correlating with their B-cell abnormality.Discussion Our findings define a novel signature of peripheral immune cells and implicate aberrant Tfh:B-cell interactions in patients with PD.AUC=area under the curve; CU=Columbia University; GWASs=Genome-wide association studies; IgG=immunoglobulin; IRBs=Institutional Review Boards; LEDD=l-dopa equivalent daily dose; MHC=major histocompatibility complex; NCs=normal controls; PBMCs=peripheral blood mononuclear cells; PC1=principal component 1; PCA=principal component analysis; PD=Parkinson disease; SN=substantia nigra; SOPs=standard operating procedures; Th=T-helper; UPA=University of Pennsylvania