Measurement of complement components in cerebral spinal fluid by radioimmunoassay in patients with multiple sclerosis

Abstract

Evidence for active immune processes occurring within the central nervous system (CNS) and involving complement has been found both in experimental animals and in humans. To examine the possible role of complement in the pathogenesis of multiple sclerosis (MS), we measured complement components C3 and C4 in cerebral spinal fluid (CSF) by the radioallergosorbent test (RAST). The method was found to be reproducible and specific. The effects of incubation time, temperature, pH of diluent, concentration of antibody used for coupling, and that of labeled anti-C3 and anti-C4 were studied. The normal range (mean ± 2 standard deviations) for CSF C4 and C3 were 0.09–0.4 and 0.46–1.4 mg/dl, respectively. The mean value of CSF C4 in neurologically normal control subjects did not differ from 45 patients; in contrast, the mean value of CSF C3 was significantly higher in MS patients. After measuring serum and CSF albumin, IgG, C3, and C4 on 20 neurologically normal subjects and on 102 coded specimens from 11 patients with MS, we calculated the rate of de novo CNS IgG, C3, and C4 synthesis. Synthesis of IgG was elevated in all patients. The measured increase in CSF C3 found in some MS patients appears in some instances to be due to an altered blood-brain barrier, and in other instances to increased CNS de novo synthesis of C3 in a manner analogous to that previously documented for CSF IgG.