Autoantibodies to glutamic acid decarboxylase in three patients with cerebellar ataxia, late-onset insulin-dependent diabetes mellitus, and polyendocrine autoimmunity
Autoantibodies to glutamic acid decarboxylase in three patients with cerebellar ataxia, late-onset insulin-dependent diabetes mellitus, and polyendocrine autoimmunity
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DOI：
10.1212/wnl.49.4.1026
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发表时间：
1997-10-01
期刊：
影响因子：
9.9
通讯作者：
Graus, F
中科院分区：
文献类型：
--
作者：
Saiz, A;Arpa, J;Graus, F
背景资料：谷氨酸脱羧酶（GAD）是僵硬人综合征（SMS）和胰岛素依赖型糖尿病（IDDM）体液自身免疫的主要靶点。GAD自身抗体（GAD-Abs）在少数小脑性共济失调患者中有报道，但其相关性尚不清楚。我们描述了三例小脑性共济失调和GAD抗体。方法：采用放射免疫分析法（RIA）和免疫组化法检测GAD-Ab，并以重组人GAD 65免疫印迹法进行验证。GAD-Ab水平的3例小脑性共济失调患者进行了比较与SMS，49与胰岛素依赖型糖尿病，64与小脑性共济失调的可能退行性起源没有相关的自身免疫功能，14个非胰岛素依赖型糖尿病胰岛细胞抗体阳性的一级亲属的胰岛素依赖型糖尿病患者，和91名正常人。结果如下：三名共济失调和GAD-Ab患者均为女性（平均年龄63岁），有孤立的进行性小脑疾病、IDDM家族史、迟发性IDDM和几种阳性血清器官特异性自身抗体。两名患者患有自身免疫性甲状腺炎，一名患有恶性贫血。脑脊液分析显示寡克隆IgG带和鞘内合成GAD-Ab。通过RIA，GAD-Ab滴度从三个病人是类似的SMS和显着高于，没有重叠，比IDDM患者的滴度。64例小脑性共济失调患者中GAD-Abs缺失，无自身免疫性疾病证据。结论：这些发现表明GAD自身免疫不仅与SMS有关，而且与小脑功能障碍有关。GAD抗体应寻求在小脑共济失调患者谁有迟发性胰岛素依赖型糖尿病和其他器官特异性自身免疫表现。
Background: Glutamic acid decarboxylase (GAD) is the main target of humoral autoimmunity in stiff-man syndrome (SMS) and insulin-dependent diabetes mellitus (IDDM). GAD autoantibodies (GAD-Abs) are reported in a few patients with cerebellar ataxia, but their relevance is unclear. We describe three patients with cerebellar ataxia and GAD-Abs. Methods: GAD-Abs were assayed by radioimmunoassay (RIA) and immunohistochemistry and confirmed by immunoblot of recombinant human GAD65. The GAD-Ab levels of the three patients with cerebellar ataxia were compared with those of five with SMS, 49 with IDDM, 64 with cerebellar ataxia of probable degenerative origin without associated autoimmune features, 14 non-IDDM islet cell antibody-positive first-degree relatives of IDDM patients, and 91 normal subjects. Results: The three patients with ataxia and GAD-Abs were women (mean age, 63 years) with an isolated progressive cerebellar disorder, family history of IDDM, late-onset IDDM, and several positive serum organ-specific autoantibodies. Two patients had autoimmune thyroiditis, and one had pernicious anemia. CSF analysis demonstrated oligoclonal IgG bands and intrathecal synthesis of GAD-Abs. By RIA, GAD-Ab titers from the three patients were similar to those of SMS and significantly higher, without overlap, than the titers of IDDM patients. GAD-Abs were absent in the 64 patients with cerebellar ataxia and no evidence of autoimmune disorders. Conclusions: These findings suggest a link of GAD autoimmunity not only with SMS but also with cerebellar dysfunction. GAD-Abs should be sought in patients with cerebellar ataxia who have late-onset IDDM and other organ-specific autoimmune manifestations.