Identification of glycoconjugates which are targets for anti-Gal(beta 1-3)GalNAc autoantibodies in spinal motor neurons

Human IgM anti-Gal(beta 1-3)GalNAc antibodies which bind to GM1 and GD1b, are implicated in the pathogenesis of predominantly motor neuropathy or motor neuron disease. By immunofluorescence microscopy, the human antibodies immunostain the surface of motor neurons from bovine spinal cord. The motor neurons are also immunostained by cholera toxin (CT), which is specific for GM1. Glycolipid analysis using thin-layer chromatography (TLC) and immunostaining reveals that the relative concentration of GM1 and GD1b in motor neurons is greatly reduced in comparison to whole spinal cord, and that other motor neuron gangliosides are unreactive with the anti-Gal(beta 1-3)GalNAc antibodies. By Western blot analysis, the antibodies react with several protein bands in motor neuron extracts, and many of the same proteins are also recognized by PNA. These data suggest that both glycoproteins and glycolipids might be targets for anti-Gal(beta 1-3)GalNAc antibodies in spinal motor neurons.