ALTERATIONS IN PLASMA COMPLEMENT LEVELS FOLLOWING HUMAN ISCHEMIC STROKE

BACKGROUND 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 following stroke. METHODS We compared peripheral blood levels of complement factor 3a (C3a), 5a (C5a) and sC5b-9 drawn from 15 patients on post-stroke days 1, 2, 3, 7, 14, 21, and 28 to age-, race/ethnicity- and gender-matched controls from the same population. Statistical analysis was performed using unpaired Mann Whitney nonparametric tests with Bonferroni correction. All data is presented as mean ± standard deviation. RESULTS Mean C3a concentrations showed significant early elevations in stroke patients relative to matched controls (controls: 1080 ± 189ng/ml; Day 1: 1609 ± 422ng/ml, P = 0.0008; Day 3: 1520 ± 317ng/ml, P = 0.0005; Day 7: 1526 ± 386ng/ml, P = 0.001). C3a was also significantly elevated on Day 28 (1448 ± 386ng/ml, P = 0.004). Prior to post-stroke 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 ± 2.1ng/ml; Day 7: 6.86 ± 3.5ng/ml, P = 0.005; Day 14: 7.65 ± 4.6ng/ml, P = 0.004). Mean sC5b-9 concentrations showed early depressions that reached significance on days 1 and 2 (controls: 275.6 ± 107ng/ml; Day 1: 167.0 ± 108ng/ml, P = 0.006; Day 2: 156.3 ± 80.0ng/ml, P = 0.005) and did not differ significantly from controls at any other time point. CONCLUSION C3a is acutely elevated following human ischemic stroke, C5a shows delayed elevations 7–14 days after cerebral ischemia and sC5b-9 is acutely depressed following stroke. Together, these data confirm complement activation following stroke and suggest that this activation is a heterogeneous process, with varying responses for different components.