Humoral mechanisms in immune neuropathies.
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.
Koski
C L
CL
Department of Neurology, University of Maryland School of Medicine, Baltimore.
D001323:Autoantibodies / Q000032:analysis*; D003167:Complement Activation / Q000276:immunology; D003711:Demyelinating Diseases / Q000276:immunology*; D006801:Humans; D009185:Myelin Proteins / Q000276:immunology*; D010525:Peripheral Nerves / Q000276:immunology; D011129:Polyradiculoneuropathy / Q000276:immunology*
D001323:Autoantibodies; D009185:Myelin Proteins