Preliminary studies on sensitization of Lewis rats with sulfated glucuronyl paragloboside

A large number of patients with peripheral neuropathy and IgM paraproteinemia have IgM monoclonal antibodies which recognize a carbohydrate determinant shared by myelin-associated glycoprotein (MAG) and sulfated glucuronyl glycolipids (SGGLs). There is considerable evidence that these IgM monoclonal antibodies are responsible for demyelination in this disorder. To study the pathogenic role of SGGLs in this type of neuropathy, we sensitized Lewis rats with sulfated glucuronyl paragloboside (SGPG), a major SGGL. Fifty percent of the animals (8/16) developed neurological symptoms such as mild to moderate distal tail tone loss, with or without abnormal posture, along with development of anti-SGPG antibodies. These antibodies reacted with SGGLs, but not with rat MAG. Morphological studies showed: (1) axonal change in the lateral aspects of the dorsal columns in the spinal cord; and (2) damage to the endothelial cells in the spinal cord which suggested a breakdown of the blood-brain barrier. There was no obvious change in the peripheral nerve. Since no marked cellular infiltration was detected in these lesions, the clinicopathological findings observed could be induced by humoral mechanism, most likely anti-SGPG antibodies.