Alterations in plasma complement levels after human ischemic stroke.
OBJECTIVE
Stroke is a leading cause of morbidity and mortality in the United States. Recent animal studies have implicated the complement system in cerebral ischemia/reperfusion injury and suggest that complement inhibition may improve stroke outcomes. To assess the applicability of these findings to humans, we evaluated the characteristics and time course of human complement activation after stroke.


METHODS
We compared peripheral blood levels of complement factor 3a (C3a), 5a (C5a), and sC5b-9 drawn from 15 patients on poststroke Days 1, 2, 3, 7, 14, 21, and 28 to age-, race/ethnicity-, and sex-matched controls from the same population. Statistical analysis was performed using unpaired Mann-Whitney nonparametric tests with Bonferroni correction. All data is presented as the mean +/- standard deviation.


RESULTS
Mean C3a concentrations showed significant early elevations in stroke patients relative to matched controls (controls: 1080 +/- 189 ng/ml; Day 1: 1609 +/- 422 ng/ml, P = 0.0008; Day 3: 1520 +/- 317 ng/ml, P = 0.0005; Day 7: 1526 +/- 386 ng/ml, P = 0.001). C3a was also significantly elevated on Day 28 (1448 +/- 386 ng/ml, P = 0.004). Before poststroke Day 7, mean C5a levels did not differ significantly from controls. However, beginning on Day 7 and continuing through Day 14, there were significant elevations in C5a (controls: 3.33 +/- 2.1 ng/ml; day 7: 6.86 +/- 3.5 ng/ml, P = 0.005; Day 14: 7.65 +/- 4.6 ng/ml, P = 0.004). Mean sC5b-9 concentrations showed early depressions that reached significance on Days 1 and 2 (controls: 275.6 +/- 107 ng/ml; Day 1: 167.0 +/- 108 ng/ml, P = 0.006; Day 2: 156.3 +/- 80.0 ng/ml, P = 0.005) and did not differ significantly from controls at any other time point.


CONCLUSIONS
C3a is acutely elevated after human ischemic stroke, C5a shows delayed elevations 7 to 14 days after cerebral ischemia, and sC5b-9 is acutely depressed after stroke. Together, these data confirm complement activation after stroke and suggest that this activation is a heterogeneous process, with varying responses for different components.
Mocco
J
J
Department of Neurological Surgery, Columbia University, New York, New York 10032, USA.
Wilson
David A
DA
Komotar
Ricardo J
RJ
Sughrue
Michael E
ME
Coates
Kristen
K
Sacco
Ralph L
RL
Elkind
Mitchell S V
MS
Connolly
E Sander
ES
D000368:Aged; D002545:Brain Ischemia / Q000150:complications*; D016022:Case-Control Studies; D003167:Complement Activation; D015926:Complement C3a / Q000378:metabolism*; D015936:Complement C5a / Q000378:metabolism*; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D020521:Stroke / Q000097:blood* / Q000209:etiology*; D013997:Time Factors
D015938:Complement Membrane Attack Complex; D015926:Complement C3a; D015936:Complement C5a