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

## TL;DR

This study finds that proteins in immune cell-derived extracellular vesicles can predict poor outcomes in stroke patients who develop infections.

## Contribution

The study identifies specific proteomic signatures in immune cell-derived EVs linked to infection and poor outcomes in ICH patients.

## Key findings

- 190 proteins showed differential abundance in EVs of infected ICH patients.
- Six proteins, including PSME1, H2B1C, MTREX, COHA1, PCSK9, and CMC1, were associated with poor outcomes and infection.
- These proteins are involved in apoptosis, DNA repair, extracellular matrix, cholesterol metabolism, and energy pathways.

## 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.

The online version contains supplementary material available at 10.1186/s12974-025-03635-9.