Objective: Compare the serum cytokine profiles and phenotypes of peripheral blood mononuclear cells (PBMCs) in a patient with Progressive Supranuclear Palsy (PSP) with his healthy twin brother.

Background: Monozygotic twins provide a valuable source of information and insight into disease mechanism, even more so in uncommon conditions like Progressive Supranuclear Palsy (PSP), an atypical type of parkinsonism with a prevalence of 5 per 100,000. In this case report, we compared the serum cytokine levels and phenotypes of peripheral blood mononuclear cells (PBMCs) isolated from a 66-year-old Caucasian man suffering from PSP with those of his healthy identical twin. Research has shown microglia are diffusely and strikingly activated in the PSP brain compared to normal controls, and are highly correlated with tau burden and areas of degeneration. Brain autopsy studies of patients with PSP have described higher expression of IL-1β, TGFβ, IL-6, and TNFα in the substantia nigra (SN) and the subthalamic nucleus (ST). Blood isolated from patients with PSP has been shown to be enriched in classical monocytes (CD16-CD32+).

Methods: Blood samples from peripheral venipuncture were obtained to measure cytokine levels and isolate PBMC. A 37-plex human cytokine/chemokine panel was utilized to detect cytokine concentrations. Flow cytometry analysis for leukocyte surface markers was performed on freshly isolated PBMC.

Results: Serum from the patient with PSP showed increases in IFNα2, TNFβ, IL-6 and IFNγ, VEGF, MCP-1, MCP-3 and BDNF when compared to his healthy twin. PBMC isolated from the patient with PSP contained a higher percentage of CD14+/CD16-/CD32+ monocytes and a very low percentage of lymphocytes. There was a decrease in the expression of the fractalkine receptor (CX3CR1) and class II MHC HLA-DR molecules on the monocyte population of the patient with PSP.

Conclusions: There is evidence of a pro-inflammatory environment (IFNα2, TNFβ, IL-6 and IFNγ) in the patient with PSP along with increased MCP-3 and MCP-1 levels that result in a concomitant increase of the monocyte population. The decrease in CX3CR1 expression suggests that monocytes may be unable to respond to fractalkine secreted by damaged neurons. It remains to be determined if this represents a cause of the PSP pathology, or if it is a long-term side effect of chronic neuroinflammation.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/leukocyte-perturbations-suggest-immune-dysregulation-in-progressive-supranuclear-palsy/