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Single-cell peripheral immunoprofiling of lewy body and Parkinson's disease in a multi-site cohort.
Phongpreecha, Thanaphong; Mathi, Kavita; Cholerton, Brenna; Fox, Eddie J; Sigal, Natalia; Espinosa, Camilo; Reincke, Momsen; Chung, Philip; Hwang, Ling-Jen; Gajera, Chandresh R; Berson, Eloise; Perna, Amalia; Xie, Feng; Shu, Chi-Hung; Hazra, Debapriya; Channappa, Divya; Dunn, Jeffrey E; Kipp, Lucas B; Poston, Kathleen L; Montine, Kathleen S; Maecker, Holden T; Aghaeepour, Nima; Montine, Thomas J.
Afiliación
  • Phongpreecha T; Department of Pathology, Stanford University, Stanford, CA, USA.
  • Mathi K; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, USA.
  • Cholerton B; Department of Biomedical Data Science, Stanford University, Stanford, CA, USA.
  • Fox EJ; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Sigal N; Department of Pathology, Stanford University, Stanford, CA, USA.
  • Espinosa C; Department of Pathology, Stanford University, Stanford, CA, USA.
  • Reincke M; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Chung P; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, USA.
  • Hwang LJ; Department of Biomedical Data Science, Stanford University, Stanford, CA, USA.
  • Gajera CR; Department of Pediatrics, Stanford University, Stanford, CA, USA.
  • Berson E; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, USA.
  • Perna A; Department of Biomedical Data Science, Stanford University, Stanford, CA, USA.
  • Xie F; Department of Pediatrics, Stanford University, Stanford, CA, USA.
  • Shu CH; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, USA.
  • Hazra D; Department of Biomedical Data Science, Stanford University, Stanford, CA, USA.
  • Channappa D; Department of Pathology, Stanford University, Stanford, CA, USA.
  • Dunn JE; Department of Pathology, Stanford University, Stanford, CA, USA.
  • Kipp LB; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, USA.
  • Poston KL; Department of Biomedical Data Science, Stanford University, Stanford, CA, USA.
  • Montine KS; Department of Pathology, Stanford University, Stanford, CA, USA.
  • Maecker HT; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, USA.
  • Aghaeepour N; Department of Biomedical Data Science, Stanford University, Stanford, CA, USA.
  • Montine TJ; Department of Pediatrics, Stanford University, Stanford, CA, USA.
Mol Neurodegener ; 19(1): 59, 2024 Aug 01.
Article en En | MEDLINE | ID: mdl-39090623
ABSTRACT

BACKGROUND:

Multiple lines of evidence support peripheral organs in the initiation or progression of Lewy body disease (LBD), a spectrum of neurodegenerative diagnoses that include Parkinson's Disease (PD) without or with dementia (PDD) and dementia with Lewy bodies (DLB). However, the potential contribution of the peripheral immune response to LBD remains unclear. This study aims to characterize peripheral immune responses unique to participants with LBD at single-cell resolution to highlight potential biomarkers and increase mechanistic understanding of LBD pathogenesis in humans.

METHODS:

In a case-control study, peripheral mononuclear cell (PBMC) samples from research participants were randomly sampled from multiple sites across the United States. The diagnosis groups comprise healthy controls (HC, n = 159), LBD (n = 110), Alzheimer's disease dementia (ADD, n = 97), other neurodegenerative disease controls (NDC, n = 19), and immune disease controls (IDC, n = 14). PBMCs were activated with three stimulants (LPS, IL-6, and IFNa) or remained at basal state, stained by 13 surface markers and 7 intracellular signal markers, and analyzed by flow cytometry, which generated 1,184 immune features after gating.

RESULTS:

The model classified LBD from HC with an AUROC of 0.87 ± 0.06 and AUPRC of 0.80 ± 0.06. Without retraining, the same model was able to distinguish LBD from ADD, NDC, and IDC. Model predictions were driven by pPLCγ2, p38, and pSTAT5 signals from specific cell populations under specific activation. The immune responses characteristic for LBD were not associated with other common medical conditions related to the risk of LBD or dementia, such as sleep disorders, hypertension, or diabetes. CONCLUSIONS AND RELEVANCE Quantification of PBMC immune response from multisite research participants yielded a unique pattern for LBD compared to HC, multiple related neurodegenerative diseases, and autoimmune diseases thereby highlighting potential biomarkers and mechanisms of disease.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Leucocitos Mononucleares / Enfermedad por Cuerpos de Lewy Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Mol Neurodegener Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Leucocitos Mononucleares / Enfermedad por Cuerpos de Lewy Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Mol Neurodegener Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos