Temporal Dynamics of Complement Activation and Outcome in Patients With Acute Ischemic Stroke

BACKGROUND: Immune-mediated inflammatory responses exacerbate brain injury and affect the prognosis in acute ischemic stroke. METHODS: We characterized longitudinal complement activation after acute ischemic stroke using serial plasma samples from 10 patients and 8 controls. Initial markers of classical (C1q), lectin (mannose-binding lectin), and alternative (complement factor Bb) pathways, as well as regulatory (complement factor H) and downstream markers (C3a, C5a, and C5b-9) were measured by ELISA at 9 time points. RESULTS: Patients with stroke showed broad complement activation, with increased C1q, mannose-binding lectin, complement factor Bb, C3a, C5a, and C5b-9, and reduced complement factor H compared with controls. Complement components showed distinct temporal patterns during follow-up. Complement factor Bb levels were lower in patients with unfavorable functional outcome and in those with moderate-to-severe stroke. C1q and C3a trajectories differed according to functional outcome, whereas C3a trajectories also differed according to stroke severity. C1q trajectories differed according to age group and infarct volume. CONCLUSIONS: These findings suggest dynamic, pathway-specific complement activation after acute ischemic stroke and highlight the need for larger studies to clarify its prognostic and therapeutic relevance.

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Publication Details

Journal
Journal of the American Heart Association
Published
2026-10-16
DOI
https://doi.org/10.1161/jaha.125.048042
Primary Topic
Complement system in diseases
Type
article
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article

Temporal Dynamics of Complement Activation and Outcome in Patients With Acute Ischemic Stroke

Jonathan M. Coutinho, Matthijs C. Brouwer, Michael W.T. Tanck, Wing Kit Man et al.
Journal of the American Heart Association
Complement system in diseases
article

Temporal Dynamics of Complement Activation and Outcome in Patients With Acute Ischemic Stroke

Jonathan M. Coutinho, Matthijs C. Brouwer, Michael W.T. Tanck, Wing Kit Man, Willeke F. Westendorp, Merijn W. Bijlsma, Inge A. Mulder, Diederik van de Beek
article en

Abstract

BACKGROUND: Immune-mediated inflammatory responses exacerbate brain injury and affect the prognosis in acute ischemic stroke. METHODS: We characterized longitudinal complement activation after acute ischemic stroke using serial plasma samples from 10 patients and 8 controls. Initial markers of classical (C1q), lectin (mannose-binding lectin), and alternative (complement factor Bb) pathways, as well as regulatory (complement factor H) and downstream markers (C3a, C5a, and C5b-9) were measured by ELISA at 9 time points. RESULTS: Patients with stroke showed broad complement activation, with increased C1q, mannose-binding lectin, complement factor Bb, C3a, C5a, and C5b-9, and reduced complement factor H compared with controls. Complement components showed distinct temporal patterns during follow-up. Complement factor Bb levels were lower in patients with unfavorable functional outcome and in those with moderate-to-severe stroke. C1q and C3a trajectories differed according to functional outcome, whereas C3a trajectories also differed according to stroke severity. C1q trajectories differed according to age group and infarct volume. CONCLUSIONS: These findings suggest dynamic, pathway-specific complement activation after acute ischemic stroke and highlight the need for larger studies to clarify its prognostic and therapeutic relevance.

Journal of the American Heart Association
Amsterdam UMC Location University of Amsterdam (NL), Amsterdam University Medical Centers (NL), University of Amsterdam (NL)
Good health and well-being
Openalex Percentile: Top 100%
Complement system in diseases
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