Elevated Plasma Complement C1Q Measured Subacutely after Traumatic Brain Injury Is Associated with Poor Functional...

Following traumatic brain injury (TBI), secondary processes, including inflammation, contribute significantly to long-term cognitive and functional impairments. Targeting these secondary processes during the subacute period after TBI represents a feasible therapeutic target. This study investigates the role of complement factor 1q (C1Q) in TBI recovery. Motivated by our rodent studies showing that thalamic inflammation post-TBI is dependent on C1Q and that blocking C1Q during the subacute period can prevent thalamic inflammation and improve aspects of TBI outcome, particularly sleep, we measured plasma C1Q levels 3-6 months post-injury in 27 patients with TBI ranging from complicated mild to severe, as well as 30 controls. TBI patients had significantly higher plasma C1Q levels (p = 0.031). We assessed the correlation between plasma C1Q and functional outcomes using the Glasgow Outcome Scale-Extended (GOSE), controlling for initial injury severity. Higher plasma C1Q levels were associated with worse functional outcomes (rho = -0.395, p = 0.046), independent of initial injury severity. These findings suggest that subacute plasma C1Q may be a novel prognostic biomarker for TBI outcomes. More importantly, subacute plasma C1Q may provide a window into ongoing, C1Q-mediated maladaptive neuroinflammatory processes after TBI that we have shown to be remediable in rodents using a safe-in-human drug that blocks C1Q. Since the initial injury cannot be changed, the ability to intervene subacutely could provide critical therapeutic benefits to the millions affected by TBI each year.