Astrocytes are a specific immunological target in Rasmussen's encephalitis
Astrocytes are a specific immunological target in Rasmussen's encephalitis
复制标题
DOI：
10.1002/ana.21148
复制
发表时间：
2007-07-01
影响因子：
11.2
通讯作者：
Bien, Christian G.
中科院分区：
文献类型：
--
作者：
Bauer, Jan;Eiger, Christian E.;Bien, Christian G.
目的：目前Rasmussen脑炎（RE）的组织病理学标准包括存在T细胞主导的炎症、小胶质细胞活化、神经元丢失和星形胶质细胞活化。然而，一项体外研究表明谷氨酸受体3（GluR 3）抗体介导的星形胶质细胞丢失。方法：应用组织化学、免疫组织化学、末端脱氧核苷酸转移酶介导的生物素-dUTP缺口末端标记和原位杂交技术对20例RE患者、6例健康对照者、6例副肿瘤性脑脊髓炎、10例阿蒙角硬化症和5例局灶性皮质发育不良患者的石蜡切片进行研究。星形胶质细胞凋亡和随后这些细胞的丢失是RE的一个具体特征。在对照组中未发现此类病变。在RE中，皮质和白色物质区域均存在星形胶质细胞凋亡和丢失。这些组织中的星形胶质细胞显示主要组织相容性复合物I类表达。此外，发现颗粒酶-B+淋巴细胞与星形胶质细胞相邻的星形胶质细胞缺陷病变密切相关。这些淋巴细胞中的颗粒酶-B+颗粒被极化并面向星形胶质细胞膜。没有证据表明抗体介导的destruction.InterpretationP：我们建议一个特定的攻击细胞毒性T淋巴细胞作为一个可能的机制，负责在RE星形胶质细胞变性。星形胶质细胞的丢失可能在神经元功能障碍、癫痫发作诱导和神经元细胞死亡的增强中起作用。
Objective: The current histopathological criteria of Rasmussen's encephalitis (RE) include the presence of T-cell-dominated inflammation, microglial activation, neuronal loss, and astrocytic activation. An in vitro study, however, suggested glutamate receptor 3 (GluR3) antibody-mediated astrocytic loss. Therefore, we investigated astrocytic apoptosis and loss in situ.Methods: Histochemical, immunohistochemical, terminal deoxynucleotidyltransferase-mediated biotin-dUTP nick end labeling and in situ hybridization techniques were applied to paraffin sections of 20 RE cases, 6 healthy control subjects, and 6 paraneoplastic encephalomyelitis, 10 Ammon's horn sclerosis, and 5 focal cortical dysplasia cases.Results: Astrocytic apoptosis and subsequent loss of these cells is a specific feature of RE. Such lesions are not found in the control groups. In RE, astrocytic apoptosis and loss was present both in cortical and in white matter areas. Astrocytes in these tissues showed major histocompatibility complex class I expression. Furthermore, granzyme-B+ lymphocytes were found in close apposition to astrocytes bordering astrocyte-deficient lesions. Granzyme-B+ granules in these lymphocytes were polarized and faced the astrocytic membranes. No evidence was found for an antibody-mediated destruction.InterpretationP: We suggest a specific attack by cytotoxic T lymphocytes as a possible mechanism responsible for astrocytic degeneration in RE. The loss of astrocytes might play a role in neuronal dysfunction, seizure induction, and enhancement of neuronal cell death.