Feline Model of Neuropathy associated with anti-MAG/SGPG antibodies

描述（由申请人提供）：与IgM副蛋白血症相关的神经病变是病因和发病机制未知的人类周围神经系统疾病。然而，许多证据指向这些疾病中组织损伤的免疫学机制。现在已经确定糖缀合物是这些神经病变的重要抗原。大约一半的IgM蛋白旁血症性神经病患者有自身抗体，可与髓鞘相关糖蛋白（MAG）和磺磺脲基副叶苷（SGPG）发生反应。尽管大量的间接证据表明抗mag /SGPG自身抗体在神经病变的发病机制中起作用，但其确切的致病作用尚不完全清楚。这部分是由于缺乏这种类型的神经病变的实验动物模型。我们假设这些疾病中的抗mag /SGPG抗体是致病的。我们将在两个具体目标中检验这一假设。目的1将通过主动免疫猫SGPG来研究抗SGPG抗体在周围神经病变中的致病作用。目的2将进一步研究抗mag /SGPG抗体在神经病变与抗mag /SGPG抗体被动转移中的作用。这些研究可能会导致抗mag /SGPG神经病变的猫模型的发展，与人类疾病非常相似

DESCRIPTION (provided by applicant): 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