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Dysregulation of the Adaptive Immune System in Patients With Early-Stage Parkinson Disease
OBJECTIVE: To determine the activation status and cytokine profiles of CD4(+) T cells, CD8(+) T cells, and CD19(+) B cells from patients with early-stage Parkinson disease (PD) compared with healthy controls (HCs). METHODS: Peripheral blood samples from 41 patients with early-stage PD and 40 HCs wer...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299515/ https://www.ncbi.nlm.nih.gov/pubmed/34301818 http://dx.doi.org/10.1212/NXI.0000000000001036 |
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author | Yan, Zhaoqi Yang, Wei Wei, Hairong Dean, Marissa N. Standaert, David G. Cutter, Gary R. Benveniste, Etty N. Qin, Hongwei |
author_facet | Yan, Zhaoqi Yang, Wei Wei, Hairong Dean, Marissa N. Standaert, David G. Cutter, Gary R. Benveniste, Etty N. Qin, Hongwei |
author_sort | Yan, Zhaoqi |
collection | PubMed |
description | OBJECTIVE: To determine the activation status and cytokine profiles of CD4(+) T cells, CD8(+) T cells, and CD19(+) B cells from patients with early-stage Parkinson disease (PD) compared with healthy controls (HCs). METHODS: Peripheral blood samples from 41 patients with early-stage PD and 40 HCs were evaluated. Peripheral blood mononuclear cells were analyzed by flow cytometry for surface markers and intracellular cytokine production. Correlations of immunologic changes and clinical parameters were analyzed. RESULTS: Adaptive immunity plays a role in the pathogenesis of PD, yet the contribution of T cells and B cells, especially cytokine production by these cells, is poorly understood. We demonstrate that naive CD4(+) and naive CD8(+) T cells are significantly decreased in patients with PD, whereas central memory CD4(+) T cells are significantly increased in patients with PD. Furthermore, IL-17–producing CD4(+) Th17 cells, IL-4–producing CD4(+) Th2 cells, and IFN-γ–producing CD8(+) T cells are significantly increased in patients with PD. Regarding B cells, we observed a decrease in naive B cells and an increase in nonswitched memory and double-negative B cells. As well, TNF-α–producing CD19(+) B cells were significantly increased in patients with PD. Notably, some of the changes observed in CD4(+) T cells and B cells were associated with clinical motor disease severity. CONCLUSIONS: These findings suggest that alterations in the adaptive immune system may promote clinical disease in PD by skewing to a more proinflammatory state in the early-stage PD patient cohort. Our study may shed light on potential immunotherapies targeting dysregulated CD4(+) T cells, CD8(+) T cells, and CD19(+) B cells in patients with PD. |
format | Online Article Text |
id | pubmed-8299515 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-82995152021-07-23 Dysregulation of the Adaptive Immune System in Patients With Early-Stage Parkinson Disease Yan, Zhaoqi Yang, Wei Wei, Hairong Dean, Marissa N. Standaert, David G. Cutter, Gary R. Benveniste, Etty N. Qin, Hongwei Neurol Neuroimmunol Neuroinflamm Article OBJECTIVE: To determine the activation status and cytokine profiles of CD4(+) T cells, CD8(+) T cells, and CD19(+) B cells from patients with early-stage Parkinson disease (PD) compared with healthy controls (HCs). METHODS: Peripheral blood samples from 41 patients with early-stage PD and 40 HCs were evaluated. Peripheral blood mononuclear cells were analyzed by flow cytometry for surface markers and intracellular cytokine production. Correlations of immunologic changes and clinical parameters were analyzed. RESULTS: Adaptive immunity plays a role in the pathogenesis of PD, yet the contribution of T cells and B cells, especially cytokine production by these cells, is poorly understood. We demonstrate that naive CD4(+) and naive CD8(+) T cells are significantly decreased in patients with PD, whereas central memory CD4(+) T cells are significantly increased in patients with PD. Furthermore, IL-17–producing CD4(+) Th17 cells, IL-4–producing CD4(+) Th2 cells, and IFN-γ–producing CD8(+) T cells are significantly increased in patients with PD. Regarding B cells, we observed a decrease in naive B cells and an increase in nonswitched memory and double-negative B cells. As well, TNF-α–producing CD19(+) B cells were significantly increased in patients with PD. Notably, some of the changes observed in CD4(+) T cells and B cells were associated with clinical motor disease severity. CONCLUSIONS: These findings suggest that alterations in the adaptive immune system may promote clinical disease in PD by skewing to a more proinflammatory state in the early-stage PD patient cohort. Our study may shed light on potential immunotherapies targeting dysregulated CD4(+) T cells, CD8(+) T cells, and CD19(+) B cells in patients with PD. Lippincott Williams & Wilkins 2021-07-22 /pmc/articles/PMC8299515/ /pubmed/34301818 http://dx.doi.org/10.1212/NXI.0000000000001036 Text en Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Article Yan, Zhaoqi Yang, Wei Wei, Hairong Dean, Marissa N. Standaert, David G. Cutter, Gary R. Benveniste, Etty N. Qin, Hongwei Dysregulation of the Adaptive Immune System in Patients With Early-Stage Parkinson Disease |
title | Dysregulation of the Adaptive Immune System in Patients With Early-Stage Parkinson Disease |
title_full | Dysregulation of the Adaptive Immune System in Patients With Early-Stage Parkinson Disease |
title_fullStr | Dysregulation of the Adaptive Immune System in Patients With Early-Stage Parkinson Disease |
title_full_unstemmed | Dysregulation of the Adaptive Immune System in Patients With Early-Stage Parkinson Disease |
title_short | Dysregulation of the Adaptive Immune System in Patients With Early-Stage Parkinson Disease |
title_sort | dysregulation of the adaptive immune system in patients with early-stage parkinson disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299515/ https://www.ncbi.nlm.nih.gov/pubmed/34301818 http://dx.doi.org/10.1212/NXI.0000000000001036 |
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