Neuropathies associated with IgM paraproteinemia are human diseases of the peripheral nervous system of unknown etiology and pathogenesis. However, much evidence points to immunological mechanisms of tissue injury in these disorders. It is now well established that glycoconjugates are important antigens in these neuropathies. About half of the patients with IgM parapraproteinemic neuropathy have autoantibodies that react with the myelin-associated glycoprotein (MAG) and sulfoglucuronyl paragloboside (SGPG). Although a large body of circumstantial evidence suggests that anti-MAG/SGPG autoantibodies play a role in the pathogenesis of neuropathy, their exact pathogenic role is not fully understood. This is in part due to the lack of an experimental animal model of this type of neuropathy. We hypothesize that anti-MAG/SGPG antibodies in these disorders are pathogenic. We will test this hypothesis in two Specific Aims.
Aim 1 will investigate the pathogenic role of anti-SGPG antibodies in peripheral neuropathy by actively immunizing cats with SGPG.
Aim 2 will further investigate the role of anti-MAG/SGPG antibodies by passive transfer of neuropathy with anti-MAG/SGPG antibodies. These studies may lead to the development of a feline model of anti-MAG/SGPG neuropathy that closely resembles the human disorder ? ? ? ?
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