Abstract WMP104: Complement System is Acutely Activated in Humans After Intracerebral Hemorrhage

Abstract

Introduction: Intracerebral hemorrhage (ICH) generates a complex local and systemic inflammatory response, but prior studies have neglected the role of the complement system. While animal models of ICH have suggested complement is a key regulator of inflammation, human data are lacking. We investigated whether the complement system was activated in ICH patients. Hypothesis: We hypothesized complement system activation product levels would be acutely elevated in ICH patients compared to matched controls. We also examined the association of these complement fragment levels with established ICH severity markers and perihematomal edema (PHE) growth rates. Methods: We identified 25 ICH patients whose blood was collected within 5 days post stroke at the University of Maryland Medical Center from June 2016 to September 2017 as part of the Recovery After Cerebral Hemorrhage (REACH) and Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS) studies. C3a, C5a, and sC5b-9 levels were measured via ELISA (Quidel, San Diego, CA) in patients and healthy controls matched for age, sex, and race. Six patients were excluded from PHE growth measurement for lack of available follow-up CT or MRI scans. Hematoma and PHE volumes were measured on the initial CT scan and the follow-up CT scan (or MRI scan if CT not done) closest to 72 hours post stroke via a semi-automated method. Results: Mean C3a (82.4 versus 49.2 ng/mL, p = 0.01), C5a (19.2 versus 9.1 ng/mL, p = 0.00005), and sC5b-9 (3000 versus 246 ng/mL, p = 0.00006) levels were elevated in ICH patients relative to matched controls. In secondary analyses, C5a level was correlated with presence of intraventricular hemorrhage (correlation coefficient 0.51, p = 0.03) and modified Graeb score (correlation coefficient 0.50, p = 0.03). Complement fragment levels were not correlated with PHE growth rates, age, ICH size, ICH location, or presence of at least 2 systemic inflammatory response syndrome (SIRS) criteria. Conclusions: Activated complement fragments C3a, C5a, and sC5b-9 are significantly (several-fold) elevated in ICH patients independently of age, ICH size, and ICH location. Considering complement’s role in initiating and augmenting inflammation, it represents a potential novel therapeutic target.