Innate and Adaptive Immunity in Parkinson Disease-P20

Increasing evidence supports the role of brain and systemic inflammation in the etiology of Parkinson disease (PD). We used gene expression profiling (RNA-seq) to examine the activation state of peripheral blood monocytes in 18 patients with early, untreated PD and 16 healthy control (HC) subjects. Monocytes were isolated by negative selection, and gene expression studied by RNA-seq and gene set enrichment analysis. A computational model that incorporated case/control status, sex, and the interaction between case/control status and sex was utilized. We found that there was a striking effect of sex on monocyte gene expression. There was inflammatory activation of monocytes in females with PD, with enrichment of gene sets associated with interferon gamma stimulation. In males, the activation patterns were more heterogeneous. These data point to the importance of systemic monocyte activation in PD, and the importance of studies which examine the differential effects of sex on pathophysiology of the disease. ]]>
Patients with early PD were diagnosed using UK Brain Bank criteria (bradykinesia and either: 4-6 Hz resting tremor or rigidity). We included male or female subjects that were within 2 years of diagnosis, who were age 30 years or older at time of PD diagnosis, and who were Hoehn and Yahr stage I-II at the time of study entry. All PD subjects had no history of prior treatment with PD medications. Other exclusion criteria for PD subjects included atypical PD syndromes due to dopamine receptor blocking drugs, metabolic disorders, encephalitis, other neurodegenerative diseases, diagnosis of vascular Parkinsonism, a clinical diagnosis of dementia, or any other medical or psychiatric condition or lab abnormality, which in the opinion of the investigator might preclude participation. Healthy controls were over 30 years old, had no current diagnosis of PD or other neurodegenerative disorder, no history of PD in first-degree blood relatives, and scored positive on no more than three items on the PD Screening Questionnaire.]]>