Infection-driven proteomic signatures in immune cell–derived extracellular vesicles reflect hemorrhagic stroke outcome

Analyzing the content of immune cell-derived extracellular vesicles (EVs) may reveal biomarkers that elucidate the mechanisms through which infection negatively affects outcomes in patients with intracerebral hemorrhage (ICH). A prospective observational study in patients with acute ICH classified by the occurrence of in-hospital infection within 7 days and outcomes at 6 months, good outcome defined as an improvement of > 10 points or > 50% in NIHSS score and a mRS score 0–2. Immune cell-derived EVs were obtained from blood samples at 7 days by immunoprecipitation with anti-CD3 (T cells), anti-CD20 (B cells) and anti-CD14 (monocytes) antibodies. The protein content of the EVs was analyzed by data independent acquisition mass spectrometry. Differential abundance between groups was defined as fold-change ≥ 2 or ≤ 0.5 and p ≤ 0.05. The study enrolled 44 patients: 17 (39%) infected, 14 (82%) with poor outcomes, and 27 (61%) with no infection, 12 (44%) with poor outcomes. There were 190 proteins with differential abundance in the EVs of infected patients, 6 relevant proteins associated with poor outcome and infection: in T cell-derived EVs PSME1 (involved in apoptosis), H2B1C and MTREX (involved in transcription regulation, DNA replication and DNA repair) were more abundant; in B cell-derived EVs, COHA1 (organization of extracellular matrix) was less abundant; and in monocyte-derived EVs, PCSK9 (cholesterol metabolism) and CMC1 (energy-related metabolic pathways) were less abundant. A cluster of proteins in immune system-derived EVs are involved in key biological pathways potentially linked to infection-related poor outcomes in patients with ICH.

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Publication Details

Journal
Journal of Neuroinflammation
Published
2025-12-04
DOI
https://doi.org/10.1186/s12974-025-03635-9
Primary Topic
Intracerebral and Subarachnoid Hemorrhage Research
Type
article
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article

Infection-driven proteomic signatures in immune cell–derived extracellular vesicles reflect hemorrhagic stroke outcome

María Alonso de Leciñana, Exuperio Díez‐Tejedor, Elisa Alonso‐López, Blanca Fuentes et al.
Journal of Neuroinflammation
Intracerebral and Subarachnoid Hemorrhage Research
article

Infection-driven proteomic signatures in immune cell–derived extracellular vesicles reflect hemorrhagic stroke outcome

María Alonso de Leciñana, Exuperio Díez‐Tejedor, Elisa Alonso‐López, Blanca Fuentes, Rodrigo Barderas, Dolores Piniella, Félix Docando, Susana B. Bravo, Laura Casado‐Fernández, Rebeca Gallego, Laura Otero‐Ortega, Fernando Laso-García, Belén Juárez-Martín, Javier Pozo-Novoa, Nerea Díaz-Gamero, María Gutiérrez-Fernández, Mari Carmen Gómez-de Frutos, Ángela Calzado-González, Mari Paz López-Molina
article en

Abstract

Analyzing the content of immune cell-derived extracellular vesicles (EVs) may reveal biomarkers that elucidate the mechanisms through which infection negatively affects outcomes in patients with intracerebral hemorrhage (ICH). A prospective observational study in patients with acute ICH classified by the occurrence of in-hospital infection within 7 days and outcomes at 6 months, good outcome defined as an improvement of > 10 points or > 50% in NIHSS score and a mRS score 0–2. Immune cell-derived EVs were obtained from blood samples at 7 days by immunoprecipitation with anti-CD3 (T cells), anti-CD20 (B cells) and anti-CD14 (monocytes) antibodies. The protein content of the EVs was analyzed by data independent acquisition mass spectrometry. Differential abundance between groups was defined as fold-change ≥ 2 or ≤ 0.5 and p ≤ 0.05. The study enrolled 44 patients: 17 (39%) infected, 14 (82%) with poor outcomes, and 27 (61%) with no infection, 12 (44%) with poor outcomes. There were 190 proteins with differential abundance in the EVs of infected patients, 6 relevant proteins associated with poor outcome and infection: in T cell-derived EVs PSME1 (involved in apoptosis), H2B1C and MTREX (involved in transcription regulation, DNA replication and DNA repair) were more abundant; in B cell-derived EVs, COHA1 (organization of extracellular matrix) was less abundant; and in monocyte-derived EVs, PCSK9 (cholesterol metabolism) and CMC1 (energy-related metabolic pathways) were less abundant. A cluster of proteins in immune system-derived EVs are involved in key biological pathways potentially linked to infection-related poor outcomes in patients with ICH.

Journal of NeuroinflammationVol. 23(1)
Universidade de Santiago de Compostela (ES), Hospital Universitario La Paz (ES), Instituto de Salud Carlos III (ES), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (ES), Hospital La Paz Institute for Health Research (ES), Unidades Centrales Científico-Técnicas (ES), HM Hospitales (ES), Camilo José Cela University (ES), Universidad Alfonso X el Sabio (ES), Instituto de Investigación Sanitaria de Santiago (ES), Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (ES), Unidad Funcional de Investigación de Enfermedades Crónicas (ES), Universidad Autónoma de Madrid (ES)
Openalex Percentile: Top 47%
Intracerebral and Subarachnoid Hemorrhage Research
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