Parkinson Disease Shown to Induce Immune Imbalance in the Blood, Indicating Possible Benefit of Immune Modulation

Researchers uncovered that patients with Parkinson disease (PD) could benefit from immune modulation as an alternative treatment, due to the condition’s influence on immune imbalance, according to findings of a study published in the journal Movement Disorders.

PD is a multisystem disease in which both the central and peripheral nervous systems are affected. The disease is characterized by the slow degeneration of the neurons in the brain due to the abnormal accumulation of a protein called α-synuclein. While it is primarily seen as a brain disorder, the behavior of immune cells in the blood of affected patients is starkly different than in those without the disease. This evidence reveals a potential extension to usual research of PD-related changes on immune response, indicating a further impact on peripheral immune cells, such as monocytes, in addition to microglia in the brain.

Researchers from the Department of Biomedicine at Aarhus University sought to investigate this understudied aspect of PD-related changes in peripheral immune cells by examining their responsiveness to stimulation and their ability to release immunomodulatory molecules, which is linked to consequences for PD progression:

• Flow cytometry was used to analyze the monocytic population in peripheral blood mononuclear cells from PD patients and healthy individuals
• Blood samples from 29 patients with PD and 20 control subjects were subjected to the protein α-synuclein
• In vitro analyses were conducted to determine response to inflammogen lipopolysaccharides and fibrillar α-synuclein by measuring the expression of CD14, CD163, and HLA-DR, and by analysis of soluble immune-related molecules in the supernatant

Study results revealed that peripheral immune cells from patients with PD had lower survival in culture, but a higher monocytic proliferative ability than control cells, indicative of shorter disease duration and late disease onset. Blood samples from patients with PD were also shown to be less responsive to stimulation, as shown by the lack of changes in CD163 and CD14 expression and by the absence of significant upregulation of anti-inflammatory cytokines in culture. In vitro analyses further showed that PD peripheral immune cells shed lower levels of soluble CD163, suggesting a less responsive monocytic population than control cells.

Researchers additionally found that some results were associated with sex, which may support a differential immune response in women versus men.

“Our data suggest that PD involves monocytic changes in blood. These cells show reduced viability and are unresponsive to specific stimuli, which might have a relevant consequence for disease progression,” said the authors.

In a press release, study author Sara Konstantin Nissen, PhD, Department of Biomedicine at Aarhus University, spoke to the potential of research in developing alternative approaches to PD treatment. “This knowledge may in the long-term lead to the development of supplementary immune-regulating treatment being combined with the current medical treatment with the drug L-dopa, which only has an effect on the brain and the symptoms,” said Nissen.

The potential impact of such a drug in targeting immune imbalance in the blood contributes to optimism among researchers that future treatments can slow down the progression of the disease. “This leads us to believe that it might be possible to, at the very least, slow down the degeneration of the neurons in the brain of Parkinson’s patients by regulating the immune system with medicine,” said Nissen.

Reference

Nissen SK, Shrivastava K, Schulte C, et al. Alterations in blood monocyte functions in Parkinson’s disease [published online August 26, 2019]. Mov Disord. doi: 10.1002/mds.27815.