Antibody of patients with Guillain-Barré syndrome mediates complement-dependent cytolysis of rat Schwann cells: Susceptibility to cytolysis reflects Schwann cell phenotype

Abstract

We previously observed that demyelination of dissociated dorsal root ganglion cultures by acute phase serum of some Guillain Barré syndrome (GBS) patients was associated with cytolysis of rat Schwann cells (SC) not committed to myelination. In this study, to determine if SC cytolysis was antibody (Ab) and complement-dependent and if SC at various stages of differentiation were uniformly susceptible, sciatic nerve SC from 1–2-day-old (SC/2d) or 6-day-old (SC/6d) Sprague Dawley rats were sensitized with IgM from GBS patients or normal controls and incubated at 37°C for 60 min with 25% guinea pig serum complement. Cytolysis was detected by vital dye exclusion. IgM Ab of 11 GBS patients induced complement-mediated cytolysis of 10.7–64.1% SC/2d (38.3 ± 18.8; mean ± SD) which was significantly higher than cytolysis of SC/6d (8.5–32%) or that by normal controls (15.0 ± 15.2 SC/2d; 8.3 ± 3.3 SC/6d mean ± SD, n = 11). Culture of SC/6d increased their cytolysis by IgM plus complement to the levels similar to that of SC/2d. FACS analysis suggested that the greater sensitivity of SC/2d to cytolysis did not reflect greater antibody binding since 2.6-fold less GBS IgM was required to initiate SC/2d lysis compared to SC/6d. This suggested that the less differentiated SC were more susceptible to complement-mediated cytolysis.