Tissue culture demyelination by normal human serum

Serum from all of 20 normal individuals induced some degree of demyelination when applied to well-myelinated mouse cerebellum cultures. An intact complement sequence through C5 is required. Demyelinating activity was heat labile at 56 degrees C for 30 minutes but was not destroyed at 50 degrees C for 30 minutes (which inhibits properdin factor B and alternate complement pathway activation, but not the classic complement pathway). Sera from patients with agammaglobulinemia, C4 deficiency, or C6 deficiency all induced demyelination. Our results suggest that tissue culture demyelination results from nonimmunoglobulin activation of the alternate complement pathway and is not limited to sera from patients with neurological disease.