Elevated plasma C4a levels in multiple sclerosis correlate with disease activity

Complement plays a pivotal role in the pathogenesis of multiple sclerosis. C4a, an activated fragment of complement component C4, has been linked to disease activity. We correlated plasma C4 and plasma and CSF C4a with clinical disease in a well-characterised cohort of patients and controls. Plasma C4 was non-significantly and CSF C4a was significantly elevated overall in patients compared to controls. Plasma C4a was raised only in acute relapse, decreasing over 2 months. Results demonstrate intrathecal and systemic activation of complement, reflected in changes in CSF and plasma C4a. The data support a role for complement activation in pathogenesis and suggest a systemic component to the disease.