Contribution of activated complements and CD59 to the pathophysiology of Rasmussen syndrome

Rasmussen syndrome (RS) is an autoimmune-associated epilepsy with refractory seizures and deteriorating motor and cognitive functions. We expect to unveil complex immunological pathophysiology from the viewpoint of complements to establish newer immunomodulatory treatments. We examined CSF levels of activated complements (iC3b, C5a and soluble membrane attack complex (sMAC)) and CD59 (inhibitor of MAC) using ELISA kits in 36 patients with RS and 44 disease controls (DCs). Disease duration from the onset of RS to CSF examination (mean ± SD) was 80.5 ± 89.7 months (n = 73). Seizure frequency at CSF examination was daily in 56, weekly in four, monthly in six, yearly in four and seizure-free in three CSF samples. The level of iC3b was significantly higher in RS than in DCs, but that of C5a, sMAC or CD59 was not different between RS and DCs. Levels of iC3b increased along with duration of disease. The ratio of patients with the levels of CD59 more than zero increased after the acute stage. Levels of CD59 in patients with daily seizure frequency were significantly lower than those with seizure control. The odds ratio between levels of CD59 and IVIg treatment by multiple linear regression analyses was significantly high. Maximum datum of activated complements or CD59 among the course of each patient was not related with final motor, cognitive and seizure outcomes. Reduction of CD59 may be one of crucial pathologies in the early stage of RS.