In vitro demyelination by serum antibody from patients with Guillain-Barré syndrome requires terminal complement complexes.
Serum from 7 patients who had acute-phase Guillain-Barré syndrome with high anti-peripheral nerve myelin antibody activity (54 to 210 units/ml) was compared with serum from 3 patients in the recovery phase (0 to 17 units/ml) and serum from 7 disease control subjects (0 to 24 units/ml) and 7 normal control subjects (0 to 7 units/ml) for its ability to demyelinate rodent dorsal root ganglion cultures. The demyelinating capacity of each serum was quantitated by counting the percent of damaged internodal segments in each of four cultures. All sera from patients in the acute phase GBS caused 50 to 78% demyelination, in contrast with 6 to 19% by the sera from all 3 patients in the recovery phase and all other control subjects. The degree of demyelination correlated with anti-peripheral nerve myelin antibody activity of the sera and demyelination was complement-dependent. Further, cultures were treated with an immunoglobulin M (IgM) fraction of an acute-phase Guillain-Barré syndrome plasma plus normal human serum depleted of complement component C7. Only those cultures treated with IgM and C7-depleted human serum reconstituted with purified C7 resulted in 50.8% demyelination, which was significantly greater than the 14.2 to 16.2% demyelination observed in the presence of heat-inactivated, C7-depleted human serum plus purified C7 or in the absence of C7 or antibody. In summary, our work suggests that anti-peripheral nerve myelin antibody in Guillain-Barré syndrome mediated complement dependent-demyelination of rodent dorsal root ganglion cultures. Further, this in vitro demyelination required generation of activation complexes of the terminal complement cascade.
Sawant-Mane
S
S
Department of Neurology, University of Maryland, Baltimore 21201.
Clark
M B
MB
Koski
C L
CL
D000208:Acute Disease; D000818:Animals; D002478:Cells, Cultured; D003184:Complement C7 / Q000276:immunology*; D015938:Complement Membrane Attack Complex / Q000276:immunology*; D003711:Demyelinating Diseases / Q000276:immunology* / Q000473:pathology; D005727:Ganglia, Spinal / Q000276:immunology / Q000473:pathology; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007700:Kinetics; D009413:Nerve Fibers, Myelinated / Q000276:immunology* / Q000473:pathology; D011129:Polyradiculoneuropathy / Q000276:immunology*; D051381:Rats; D013194:Staining and Labeling
D003184:Complement C7; D015938:Complement Membrane Attack Complex; D007106:Immune Sera; D007075:Immunoglobulin M