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Journal of the American Heart AssociationNeurosciencePeer-reviewed journal article

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

Yan WangiD, Willeke F. WestendorpiD, Merijn W. BijlsmaiD, Michael W.T. TanckiD, Wing Kit Man, Matthijs C. BrouweriD, Inge A. MulderiD, Jonathan M. CoutinhoiD, Diederik van de BeekiD

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Abstract

Immune-mediated inflammatory responses exacerbate brain injury and affect the prognosis in acute ischemic stroke (AIS). We characterized longitudinal complement activation after AIS using serial plasma samples from 10 patients and 8 controls. Initial markers of classical (C1q), lectin (mannose-binding lectin [MBL]), and alternative (Factor Bb [CFBb]) pathways, as well as regulatory (Factor H [CFH]) and downstream markers (C3a, C5a and C5b-9) were measured by ELISA at 9 time points. Stroke patients showed broad complement activation with increased C1q, MBL, CFBb, C3a, C5a, and C5b-9, and reduced CFH. C1q, MBL, and CFBb peaked around day 17. MBL was higher in patients with poor outcome, CFBb was higher with good outcome, and C5b-9 in severe strokes. These findings reveal pathway-specific complement dynamics after AIS and support complement as a target for stage-specific therapy.

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