Autoimmune mechanisms in peripheral neuropathies.
In certain patients with demyelinating neuropathy and plasma cell dyscrasia, there are IgM monoclonal antibodies that recognize a carbohydrate epitope shared by myelin-associated glycoprotein (MAG) and at least two acidic glycolipids in the peripheral nervous system (PNS). The structures of the two acidic lipids have been elucidated as a new class of glycosphingolipids, termed sulfoglucuronyl glycolipids (SGGLs). SGGLs have been demonstrated to be present in myelin, axolemma, and other glia-related membranes in PNS of several animal species, as well as in human dorsal root ganglia and sympathetic ganglia. In rabbits sensitized with sulfoglucuronyl paragloboside (SGPG), a major SGGL in PNS, antibodies developed with reactivities toward SGPG and MAG. The animals also showed moderate weakness, a slowed nerve conduction velocity, and evidence of conduction block. Recently we also found SGPG in rat brain microvessels. This finding supports our hypothesis that autoantibodies may first interact with endothelial cell-bound antigens and that this might change the permeability of the blood-brain or blood-nerve barrier to permit the entry of these autoantibodies into the nervous system. Our data are consistent with the concept that an autoimmune response against the sulfoglucuronyl residue may participate in the pathogenesis of immune-mediated neuropathy.
Yu
R K
RK
Department of Biochemistry and Molecular Biophysics, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0614.
Ariga
T
T
Kohriyama
T
T
Kusunoki
S
S
Maeda
Y
Y
Miyatani
N
N
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D006028:Glycosphingolipids / Q000276:immunology*; D006801:Humans; D010523:Peripheral Nervous System Diseases / Q000276:immunology*; D011129:Polyradiculoneuropathy / Q000276:immunology*
D006028:Glycosphingolipids