Adaptive Immunity Alterations May Promote Disease Activity in Parkinson Disease

Abnormalities in peripheral adaptive immune cells may fuel initiation and progression of Parkinson disease (PD) via enhanced immune cell infiltration and neuroinflammation in the central nervous system, according to study findings published in Neurology: Neuroimmunology & Neuroinflammation.

While it has been established that adaptive immunity has a role in PD pathogenesis, there is currently a lack of clear understanding regarding the role of T and B cells, particularly the cytokines produced by these cells, in the disease.

To improve this understanding, study researchers evaluated peripheral blood samples from patients with early-stage PD (n=41) and healthy controls (n=45). They utilized flow cytometry to analyze peripheral blood mononuclear cells for surface markers and intracellular cytokine production. Additionally, study investigators analyzed relationships of clinical parameters and immunologic alterations.

They stained peripheral blood samples with CD45, CD3, CD4, CD8, CCR7, and CD45RA. Findings indicated a significant decrease of CCR7⁺CD45RA⁺-naïve CD4⁺ T cells and a significant increase in CCR7⁺CD45RA⁻ central memory (TCM) CD4⁺ T cells in patients with PD vs healthy controls.

Patients who had elevated CD4⁺ TCM cells had worsening of their Movement Disorder Society Parkinson Disease Rating Scale scores.

Additionally, study researchers observed a significant increase in interleukin (IL) 17–producing CD4⁺ Th17 cells, IL-4-producing CD4⁺ Th2 cells, and IFN-γ-producing CD8⁺ T cells in patients with PD relative to healthy controls. “Thus, the increase in IFN- γ–producing cytotoxic CD8⁺ T cells may contribute to both neuroinflammation and neuronal damage in patients with PD,” wrote the researchers.

There was also a reduction in naïve B cells as well as an increase in nonswitched memory and double-negative B cells. Tumor necrosis factor α–producing CD19⁺ B cells were also significantly elevated in the PD samples.

A limitation of this study was the lack of a long-term follow-up. As such, the researchers were unable to assess longitudinal immune phenotypes or disease progression in patients with PD vs healthy controls.

Based on their findings, the study researchers concluded that their findings “may shed light on potential immunotherapies targeting dysregulated CD4⁺ T cells, CD8⁺ T cells, and CD19⁺ B cells in patients with PD.”

Reference

Yan Z, Yang W, Wei H, et al. Dysregulation of the adaptive immune system in patients with early-stage Parkinson disease. Neurol Neuroimmunol Neuroinflamm. 2021;8(5):e1036. doi:10.1212/NXI.0000000000001036