Antibody and
complement are implicated in the pathogenesis of a number of human, primarily demyelinating neuropathies. The ability of serum and purified, primarily
IgM,
antibodies to mediate
demyelination was demonstrated in both in vitro and in vivo model systems. Complement activation to produce channel-forming terminal
complement complexes,
C5b-8 and
C5b-9, was required for
demyelination in vitro.
Antibodies implicated in the
demyelination of peripheral nerve of GBS patients and patients with
monoclonal gammopathy-associated neuropathy bind
carbohydrate epitopes on various neutral or acidic
glycolipids and
glycoproteins of peripheral nerve. In acute monophasic GBS,
antibodies of multiple specificities may be induced to different infectious agents. These Ab, following penetration of a damaged blood-nerve barrier, are proposed to bind determinants of human peripheral nerve and participate in
demyelination of nerve through activation of
complement. These
antibodies correlate with the
clinical course, the generation of complement activation products, and the response to
plasmapheresis. The mechanism by which the blood-nerve barrier is broken in GBS and other inflammatory demyelinating neuropathies and the extent of the role of the cellular immune system remain to be determined. Recent experiments demonstrated that T cells, antibody, and
complement could synergistically contribute to central nervous system
demyelination in naive rats. A similar synergism would be an attractive hypothesis for
demyelination in the peripheral nervous system.