TY - UNPB
T1 - Early-to-mid idiopathic Parkinson’s disease shows a more cytotoxic but declined CD8-regulatory peripheral immune profile
AU - Capelle, Christophe
AU - Cire, Séverine
AU - Hansen, Maxime
AU - Pavelka, Lukas
AU - Hedin, Fanny
AU - Konstantinou, Maria
AU - Revets, Dominique
AU - Tslaf, Vera
AU - Marques, Taina
AU - Baron, Alexandre
AU - Domingues, Olivia
AU - Zeng, Ni
AU - May, Patrick
AU - Cosma, Antonio
AU - Balling, Rudi
AU - Krüger, Rejko
AU - Ollert, Markus
AU - Hefeng, Feng Q.
N1 - Acknowledgements
We first would like to show our gratitude to all the participants of the Luxembourg Parkinson’s Study cohort for their participation in this clinical research study. We thank the recruitment team and study nurses of Parkinson Research Clinic of CHL and the Clinical and Epidemiological Investigation Centre (CIEC) of LIH for their excellent support, especially Daniela Valoura Esteves for the coordination of the recruitment of healthy controls. We also highly appreciate the expert support of the processing and biorepository teams at the Integrated Biobank of Luxembourg (IBBL). This study was mainly supported by the Luxembourg Personalized Medicine Consortium (PMC) (CoPImmunoPD, PMC/2018/01, F.Q.H.). The study was also partially supported by Luxembourg National Research Fund (FNR) CORE programme grant (CORE/14/BM/8231540/GeDES, F.Q.H.), FNR AFR-RIKEN bilateral programme (TregBAR, 11228353, F.Q.H., R.B. and M.O.) and several PRIDE programme grants (PRIDE/11012546/NEXTIMMUNE, PRIDE/10907093/CRITICS and PRIDE/14254520/i2TRON, F.Q.H., R.K., M.O.) and an individual AFR grant (PDH-2015-1/9989160, N.Z. via the group of F.Q.H.). The Luxembourg Parkinson’s study is funded within the National Centre of Excellence in Research on Parkinson’s disease (NCER-PD) by FNR. The work of R.K. was further supported by an Excellence Grant in Research within the PEARL programme of the FNR. Some icons in Figure 1A were generated from BioRender.com.
PY - 2022/7/22
Y1 - 2022/7/22
N2 - Parkinson’s disease (PD) is the second most common neurodegenerative disease. Brain neuroinflammation plays a role in PD pathogenesis. However, the involvement of the peripheral immune system has not been systematically investigated. Here we analyzed >700 combinatorial immunological features in fresh blood of 28 early-to-mid-stage PD patients and 24 matched controls. We found an enhanced cytotoxic immune profile in idiopathic PD patients (iPD), with a higher frequency of terminally-differentiated effector CD8 T (TEMRA), late-differentiated CD8+ natural killer T cells and neutrophils. This immune profile was intensified by elevated serum granzyme A, reduced percentages of CD8+FOXP3+ regulatory T cells and group 2 innate lymphoid cells with immunosuppressive or tolerance-inducing functions. The frequency of CD8 TEMRA was negatively correlated with disease duration, suggesting a contribution to PD pathogenesis. Our work provides a comprehensive map on disturbed peripheral adaptive and innate immune cells in early-to-mid iPD, proposing easily-accessible candidates for early diagnosis and treatments.
AB - Parkinson’s disease (PD) is the second most common neurodegenerative disease. Brain neuroinflammation plays a role in PD pathogenesis. However, the involvement of the peripheral immune system has not been systematically investigated. Here we analyzed >700 combinatorial immunological features in fresh blood of 28 early-to-mid-stage PD patients and 24 matched controls. We found an enhanced cytotoxic immune profile in idiopathic PD patients (iPD), with a higher frequency of terminally-differentiated effector CD8 T (TEMRA), late-differentiated CD8+ natural killer T cells and neutrophils. This immune profile was intensified by elevated serum granzyme A, reduced percentages of CD8+FOXP3+ regulatory T cells and group 2 innate lymphoid cells with immunosuppressive or tolerance-inducing functions. The frequency of CD8 TEMRA was negatively correlated with disease duration, suggesting a contribution to PD pathogenesis. Our work provides a comprehensive map on disturbed peripheral adaptive and innate immune cells in early-to-mid iPD, proposing easily-accessible candidates for early diagnosis and treatments.
U2 - 10.21203/rs.3.rs-1834770/v1
DO - 10.21203/rs.3.rs-1834770/v1
M3 - Preprint
BT - Early-to-mid idiopathic Parkinson’s disease shows a more cytotoxic but declined CD8-regulatory peripheral immune profile
ER -