Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Neurology. 2011 Nov 1;77(18):1698-701. doi: 10.1212/WNL.0b013e3182364a44. Epub 2011 Oct 19.
To report the metabotropic glutamate receptor 5 (mGluR5) as the autoantigen of antibodies from 2 patients with Hodgkin lymphoma (HL) and limbic encephalopathy (Ophelia syndrome).
Immunohistochemistry with brain tissue and cultures of rat hippocampal neurons were used to demonstrate antibodies. Immunoprecipitation, mass spectrometry, and mGluR5-null mice served to identify the antigen. HEK293 cells transfected with mGluR5 or mGluR1 were used to determine immunologic crossreactivity.
Both patients developed symptoms consistent with limbic encephalopathy; one had MRI findings typical of this disorder and the other had more extensive radiologic involvement, including parietal and occipital cortex. Patients' sera had antibodies that predominantly reacted with the neuropil of hippocampus and cell surface of live hippocampal neurons. Immunoprecipitation from cultured neurons and mass spectrometry demonstrated that the antigen was mGluR5, a receptor involved in processes of learning and memory. The reactivity of patients' sera was abrogated in brain of mGluR5-null mice, further confirming the antibody specificity. Studies with a large number of controls including 2 patients with cerebellar ataxia and mGluR1 antibodies showed that mGluR5 was only identified by sera of the 2 patients with the Ophelia syndrome, and that despite the homology of this receptor with mGluR1 each autoantigen was specific for a distinct syndrome.
Antibodies to mGluR5 should be considered in patients with symptoms of limbic encephalitis and HL (Ophelia syndrome). Recognition of this disorder is important because it can affect young individuals and is reversible.
报告代谢型谷氨酸受体 5（mGluR5）是 2 例霍奇金淋巴瘤（HL）和边缘性脑炎（奥菲莉亚综合征）患者抗体的自身抗原。
使用脑组织和大鼠海马神经元培养物的免疫组织化学方法来证明抗体的存在。免疫沉淀、质谱分析和 mGluR5 基因敲除小鼠用于鉴定抗原。转染 mGluR5 或 mGluR1 的 HEK293 细胞用于确定免疫交叉反应性。
两名患者均出现符合边缘性脑炎的症状；其中一名患者的 MRI 检查结果具有该疾病的典型特征，另一名患者的影像学受累更广泛，包括顶叶和枕叶皮质。患者的血清中存在主要与海马神经突和活海马神经元细胞表面反应的抗体。从培养神经元中免疫沉淀和质谱分析表明，抗原是 mGluR5，这是一种参与学习和记忆过程的受体。患者血清的反应性在 mGluR5 基因敲除小鼠的脑中被消除，进一步证实了抗体的特异性。对包括小脑共济失调和 mGluR1 抗体的 2 例患者在内的大量对照研究表明，只有 2 例奥菲莉亚综合征患者的血清中识别出 mGluR5，并且尽管该受体与 mGluR1 具有同源性，但每种自身抗原都针对特定的综合征。
对于出现边缘性脑炎和 HL（奥菲莉亚综合征）症状的患者，应考虑抗 mGluR5 抗体。认识到这种疾病很重要，因为它会影响年轻人，而且是可逆的。
