Peripheral Immune pattern in a genetic cohort of p.A53T alpha-synuclein carriers

Abstract

Introduction: Previous research has shown that inflammatory immune biomarkers including peripheral white blood cell subpopulations differ between Parkinson's disease (PD) patients and healthy controls (HC), with PD exhibiting higher neutrophil to lymphocyte ratio (NLR). The aim of the present report was to assess the peripheral immune profile in patients or asymptomatic carriers harboring the p.A53T alpha-synuclein (SNCA) mutation.

Methods: Data regarding 31 p.A53T SNCA PD patients, 9 asymptomatic mutation carriers and 194 HCs were obtained from the database of the Parkinson's Progression Markers Initiative (PPMI). Focus was placed on peripheral immune blood cells subpopulations and clinical/imaging parameters at baseline.

Results: NLR, Absolute Neutrophil cell count and Neutrophils to total Leukocytes ratio were increased in the p.A53T SNCA PD group as compared to HCs [2.77 vs 2.18 (p < 0.001), 4.32 × 10^3 cells/μL vs 3.67 × 10^3 cells/μL (p = 0.001), 65.67 % vs 59.55 % (p < 0.001)]. Differences in NLR were mainly driven by the male patient subgroup. Lymphocytes to total Leukocytes and Monocytes to total Leukocytes ratio were lower in the p.A53T SNCA cohort as compared to HC [(p = 0.001) and (p = 0.002)]. Finally, we observed a positive correlation between the absolute Lymphocyte count and the mean putamen DATSCAN signal. Asymptomatic carriers did not differ statistically from either group.

Discussion: Our current study provides evidence of a specific pattern of peripheral immune response in the p.A53T SNCA PD group which aligns well with literature data in idiopathic and GBA-PD. Whether this peripheral immune activation represents a contributing cause or an effect of the neurodegenerative process will require further study.

Keywords: Asymptomatic carriers; Leukocyte subpopulations; Neuroinflammation; Neutrophil–lymphocyte ratio; Parkinson's disease; Peripheral immunity.