Gahring L C, Rogers S W, Twyman R E
Geriatric Research, Education and Clinical Center (GRECC), VA Medical Center, Salt Lake City, UT 84112, USA.
Neurology. 1997 Feb;48(2):494-500. doi: 10.1212/wnl.48.2.494.
We describe a 63-year-old man with a 5-year history of progressive sporadic olivopontocerebellar atrophy (OPCA) who exhibits high serum titers of IgM autoantibodies to the neuronal glutamate receptor subunit GluR2. Immunohistochemistry revealed intense staining of mouse cerebellar Purkinje cells and cells in the pontine nuclei and olivary complex. Glutamate receptor currents were activated in a subset of cultured mouse neurons by an anti-GluR2 IgM fraction, and they were blocked by the competitive AMPA-type glutamate receptor antagonist CNQX and by a synthetic peptide to a specific epitope region of GluR2 (AA 369-393). The patient was treated with nine courses of plasmapheresis with little improvement of symptomatology. However, IgM titers to GluR2 decreased approximately 8-fold and the serum functional activity decreased proportionally. These findings may suggest a role for autoimmunity to glutamate receptors in the pathophysiology of certain forms of progressive nervous system degeneration.
我们描述了一名63岁男性，患有进行性散发性橄榄脑桥小脑萎缩（OPCA）5年，其血清中抗神经元谷氨酸受体亚基GluR2的IgM自身抗体滴度很高。免疫组织化学显示小鼠小脑浦肯野细胞以及脑桥核和橄榄复合体中的细胞有强烈染色。抗GluR2 IgM组分在一部分培养的小鼠神经元中激活了谷氨酸受体电流，并且它们被竞争性AMPA型谷氨酸受体拮抗剂CNQX以及针对GluR2特定表位区域（氨基酸369 - 393）的合成肽所阻断。该患者接受了9个疗程的血浆置换治疗，症状改善甚微。然而，针对GluR2的IgM滴度下降了约8倍，血清功能活性也相应降低。这些发现可能提示自身免疫对谷氨酸受体在某些形式的进行性神经系统变性的病理生理学中起作用。
