Sex-specific immune-biological profiles in Parkinson's disease.

Depending on age, both the risk and characteristics of Parkinson's disease (PD) differ between the sexes. The immune system might have a role; however, human-based evidence remains scarce. Here, we investigated the relationship between peripheral immune cellular composition and the clinical-biological sexual dimorphism of PD. The leukocyte population count (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), the neutrophil-to-lymphocyte ratio (NLR), and the monocytes-to-lymphocytes ratio (MLR) were collected and compared in 117 PD patients and 86 controls (CTLs), and then related to blood levels of sex hormones, CSF markers of neurodegeneration (α-synuclein, amyloid-β-42, amyloid-β-40, total tau, and phosphorylated-181-tau), and clinical features in male and female PD patients. Finally, a cluster analysis based on the three main leukocyte populations (neutrophils, lymphocytes, monocytes) was performed for the entire PD cohort. Male PD patients had lower lymphocyte counts and higher NLR than male CTLs. Females with PD had lower monocyte counts, NLR, and MLR than males with PD. Lymphocyte counts correlated with cognition in male, but not female, PD patients. Finally, two clusters of peripheral immune cellular composition were identified: the "high peripheral inflammation" one, mostly comprising male patients, with worse clinical features and greater central α-synuclein burden, and the "low peripheral inflammation cluster", which mainly comprised female patients, with milder clinical features and lower central synucleinopathy. In conclusion, the peripheral immune pattern entails sex-specific clinical-biological profiles in PD. Moreover, systemic inflammation clusters with sex, sexual hormones, clinical features, and central synucleinopathy in PD, supporting the relevance of immunity in sexual dimorphism of the disease.