Peripheral immune pattern in a genetic cohort of p.A53T Alpha-Synuclein carriers.
Koros, C.; Simitsi, A. M.; Papagiannakis, N.; Antonelou, R.; Bougea, A.; Papadimitriou, D.; Pachi, I.; Beratis, I.; Kontaxopoulou, D.; Fragkiadaki, S.; Sfikas, E.; Alefanti, I.; Chrysovitsanou, C.; Angelopoulou, E.; Bregianni, M.; Lourentzos, K.; Constantinides, V. C.; Velonakis, G.; Prasopoulos, V.; Bonakis, A.; Papageorgiou, S. G.; Potagas, C.; Picillo, M.; Barone, P.; Stamelou, M.; Stefanis, L.
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IntroductionPrevious research has shown that inflammatory immune biomarkers including peripheral white blood cell subpopulations differ between Parkinsons disease (PD) patients and healthy controls (HC), with idiopathic PD exhibiting higher neutrophil to lymphocyte ratio (NLR). The aim of our present report was to assess the peripheral immune profile in patients or asymptomatic carriers harboring the p.A53T alpha-synuclein (SNCA) mutation. MethodsData regarding 31 p.A53T SNCA PD patients, 9 asymptomatic mutation carriers and 194 HCs were obtained from the database of the Parkinsons Progression Markers Initiative (PPMI). Focus was placed on peripheral immune blood cells subpopulations and clinical/imaging parameters during the initial study assessment. ResultsNLR, Absolute Neutrophil cell count and Neutrophil 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), 4,32x10^3 cells/L vs 3,67x 10^3 cells/L (p=0.001), 65,67% vs 59,55% (p<0.001) respectively]. Differences in NLR were mainly driven by the male patient subgroup. The absolute Lymphocyte cell count showed a trend towards being decreased in p.A53T PD, and Lymphocyte to total leukocytes ratio was lower in p.A53T SNCA cohort as compared to HC [26,16% vs 30,02% (p=0.001)]. Monocyte to total Leukocytes ratio was lower in p.A53T PD 5,49% vs 6,74% (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 p.A53T SNCA PD or HC regarding leucocyte subpopulations counts. DiscussionOur 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 other genetic PD forms. Furthermore, given former evidence that alpha-synuclein represents an immune target in PD, we can speculate a putative underlying inflammatory pathway in this archetypal form of genetic synucleinopathy.
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