Immune Cell Distributions in the Blood of Healthy Individuals at High Genetic Risk of Parkinson’s Disease

Laura Deecke; David Goldeck; Olena Ohlei; Jan Homann; Ilja Demuth; Lars Bertram; Graham Pawelec; Christina M. Lill

doi:10.3390/ijms252413655

Immune Cell Distributions in the Blood of Healthy Individuals at High Genetic Risk of Parkinson’s Disease

Laura Deecke, David Goldeck, Olena Ohlei, Jan Homann, Ilja Demuth, Lars Bertram, Graham Pawelec, Christina M. Lill^*

^*Korrespondierende/r Autor/-in für diese Arbeit

Institut für Neurogenetik

3 Zitate (Scopus)

Abstract

The immune system likely plays a key role in Parkinson’s disease (PD) pathophysiology. Thus, we investigated whether immune cell compositions are already altered in healthy individuals at high genetic risk for PD. We quantified 92 immune cell subtypes in the blood of 442 individuals using multicolor flow cytometry. Polygenic risk scores (PGS) for PD were calculated based on genome-wide significant SNPs (n = 87) from a large genome-wide association study (n = 1,530,403). Linear regression analyses did not reveal significant associations between PGS and any immune cell subtype (FDR = 0.05). Nominally significant associations were observed for NKG2C+ B cells (p = 0.026) in the overall sample. Older participants at increased genetic PD risk also showed a higher proportion of myeloid dendritic cells (p = 0.019) and CD27+CD4+ memory T cells (p = 0.043). Several immune cells were nominally statistically associated in women only. These findings suggest that major alterations of immune cells only occur later in the progression of PD.

Originalsprache	Englisch
Aufsatznummer	13655
Zeitschrift	International Journal of Molecular Sciences
Jahrgang	25
Ausgabenummer	24
ISSN	1661-6596
DOIs	https://doi.org/10.3390/ijms252413655
Publikationsstatus	Veröffentlicht - 12.2024

Fördermittel

The BASE-II research project (co-PIs: Lars Bertram, Ilja Demuth, Denis Gerstorf, Ulman Lindenberger, Graham Pawelec, Elisabeth Steinhagen-Thiessen, and Gert G. Wagner) has been supported by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) under grant numbers #16SV5536K, #16SV5537, #16SV5538, #16SV5837, #01UW0808, #01GL1716A, and #01GL1716B, and by the Max Planck Institute for Human Development, Berlin, Germany. Additional contributions (e.g., equipment, logistics, personnel) were made from each of the other participating sites. The responsibility for the contents of this publication lies with its authors. C.M.L. was supported by the Heisenberg program of the German Research Foundation (DFG; LI 2654/4-1).

Träger	Trägernummer
Max-Planck-Gesellschaft
Bundesministerium für Bildung und Forschung	16SV5536K, 01GL1716B, 01GL1716A, 01UW0808, 16SV5538, 16SV5537, 16SV5837
Deutsche Forschungsgemeinschaft	LI 2654/4-1

UN SDGs

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

SDG 3 – Gesundheit und Wohlergehen

Strategische Forschungsbereiche und Zentren

Querschnittsbereich: Medizinische Genetik

DFG-Fachsystematik

2.23-06 Molekulare und zelluläre Neurologie und Neuropathologie

Dokumente

10.3390/ijms252413655

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title = "Immune Cell Distributions in the Blood of Healthy Individuals at High Genetic Risk of Parkinson{\textquoteright}s Disease",

abstract = "The immune system likely plays a key role in Parkinson{\textquoteright}s disease (PD) pathophysiology. Thus, we investigated whether immune cell compositions are already altered in healthy individuals at high genetic risk for PD. We quantified 92 immune cell subtypes in the blood of 442 individuals using multicolor flow cytometry. Polygenic risk scores (PGS) for PD were calculated based on genome-wide significant SNPs (n = 87) from a large genome-wide association study (n = 1,530,403). Linear regression analyses did not reveal significant associations between PGS and any immune cell subtype (FDR = 0.05). Nominally significant associations were observed for NKG2C+ B cells (p = 0.026) in the overall sample. Older participants at increased genetic PD risk also showed a higher proportion of myeloid dendritic cells (p = 0.019) and CD27+CD4+ memory T cells (p = 0.043). Several immune cells were nominally statistically associated in women only. These findings suggest that major alterations of immune cells only occur later in the progression of PD.",

author = "Laura Deecke and David Goldeck and Olena Ohlei and Jan Homann and Ilja Demuth and Lars Bertram and Graham Pawelec and Lill, \{Christina M.\}",

note = "Publisher Copyright: {\textcopyright} 2024 by the authors.",

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doi = "10.3390/ijms252413655",

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T1 - Immune Cell Distributions in the Blood of Healthy Individuals at High Genetic Risk of Parkinson’s Disease

AU - Deecke, Laura

AU - Goldeck, David

AU - Ohlei, Olena

AU - Homann, Jan

AU - Demuth, Ilja

AU - Bertram, Lars

AU - Pawelec, Graham

AU - Lill, Christina M.

PY - 2024/12

Y1 - 2024/12

N2 - The immune system likely plays a key role in Parkinson’s disease (PD) pathophysiology. Thus, we investigated whether immune cell compositions are already altered in healthy individuals at high genetic risk for PD. We quantified 92 immune cell subtypes in the blood of 442 individuals using multicolor flow cytometry. Polygenic risk scores (PGS) for PD were calculated based on genome-wide significant SNPs (n = 87) from a large genome-wide association study (n = 1,530,403). Linear regression analyses did not reveal significant associations between PGS and any immune cell subtype (FDR = 0.05). Nominally significant associations were observed for NKG2C+ B cells (p = 0.026) in the overall sample. Older participants at increased genetic PD risk also showed a higher proportion of myeloid dendritic cells (p = 0.019) and CD27+CD4+ memory T cells (p = 0.043). Several immune cells were nominally statistically associated in women only. These findings suggest that major alterations of immune cells only occur later in the progression of PD.

AB - The immune system likely plays a key role in Parkinson’s disease (PD) pathophysiology. Thus, we investigated whether immune cell compositions are already altered in healthy individuals at high genetic risk for PD. We quantified 92 immune cell subtypes in the blood of 442 individuals using multicolor flow cytometry. Polygenic risk scores (PGS) for PD were calculated based on genome-wide significant SNPs (n = 87) from a large genome-wide association study (n = 1,530,403). Linear regression analyses did not reveal significant associations between PGS and any immune cell subtype (FDR = 0.05). Nominally significant associations were observed for NKG2C+ B cells (p = 0.026) in the overall sample. Older participants at increased genetic PD risk also showed a higher proportion of myeloid dendritic cells (p = 0.019) and CD27+CD4+ memory T cells (p = 0.043). Several immune cells were nominally statistically associated in women only. These findings suggest that major alterations of immune cells only occur later in the progression of PD.

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DO - 10.3390/ijms252413655

M3 - Journal articles

C2 - 39769417

AN - SCOPUS:85213228349

SN - 1661-6596

VL - 25

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 24

M1 - 13655

ER -

Immune Cell Distributions in the Blood of Healthy Individuals at High Genetic Risk of Parkinson’s Disease

Abstract

Fördermittel

UN SDGs

Strategische Forschungsbereiche und Zentren

DFG-Fachsystematik

Dokumente

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Fingerprint

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