Patients with acute ischemic stroke showed broad, dynamic, pathway-specific complement activation over time compared with controls, with complement factor Bb, C1q, and C3a differing by outcome, severity, age, or infarct volume, highlighting the need for larger studies to clarify prognostic and therapeutic relevance.
Key Findings
Results
Patients with acute ischemic stroke showed broad complement activation compared with controls.
Serial plasma samples were analyzed from 10 stroke patients and 8 controls.
Patients had increased C1q, mannose-binding lectin, complement factor Bb, C3a, C5a, and C5b-9 compared with controls.
Patients had reduced complement factor H compared with controls.
Markers covered the classical (C1q), lectin (MBL), and alternative (factor Bb) pathways, a regulator (factor H), and downstream markers (C3a, C5a, C5b-9).
Results
Different complement components showed distinct temporal patterns during follow-up after stroke.
Complement markers were measured by ELISA at 9 time points.
The abstract reports distinct temporal patterns for the individual components, suggesting dynamic, pathway-specific activation.
Results
Complement factor Bb levels were lower in patients with unfavorable functional outcome and in those with moderate-to-severe stroke.
Factor Bb is a marker of the alternative pathway.
Comparisons were between outcome groups (favorable vs unfavorable functional outcome) and stroke severity groups within the 10 patients.
Results
C1q and C3a trajectories differed according to functional outcome.
C1q is a classical pathway marker and C3a a downstream activation product.
The differences were in longitudinal trajectories over the 9 time points.
Results
C3a trajectories differed according to stroke severity.
C3a trajectories differed by stroke severity in addition to functional outcome.
Results
C1q trajectories differed according to age group and infarct volume.
C1q is a classical pathway marker.
Trajectory differences were observed across age groups and infarct volume categories.
Conclusions
The authors conclude that complement activation after stroke is dynamic and pathway-specific, and that larger studies are needed.
The sample was small (10 patients, 8 controls).
The authors state that larger studies are needed to clarify prognostic and therapeutic relevance.
What This Means
This small study tracked how the body's complement system, a part of the immune system that drives inflammation, changes over time after an ischemic stroke (a stroke caused by a blocked blood vessel in the brain). Researchers took repeated blood samples at 9 time points from 10 stroke patients and compared them with samples from 8 people without stroke.
Patients with stroke showed widespread complement activation, with higher levels of several complement proteins from different branches of the system and lower levels of a protective regulatory protein (factor H). The different proteins rose and fell in different patterns over time. Some patterns were linked to outcomes: factor Bb was lower in patients with worse functional recovery and more severe stroke, and the time courses of C1q and C3a differed by recovery, stroke severity, age, or infarct size.
Because only 10 patients and 8 controls were studied, these results are preliminary. This research suggests complement activation after stroke is complex and varies by pathway and over time, and that it may relate to outcomes. Larger studies would be needed to find out whether these markers could help predict recovery or guide treatments.
Wang Y, Westendorp W, Bijlsma M, Tanck M, Man W, Brouwer M, et al.. (2026). Temporal Dynamics of Complement Activation and Outcome in Patients With Acute Ischemic Stroke.. Journal of the American Heart Association. https://doi.org/10.1161/JAHA.125.048042