Neurologic syndromes related to anti-GAD65 Clinical and serologic response to treatment
Neurologic syndromes related to anti-GAD65 Clinical and serologic response to treatment
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DOI：
10.1212/nxi.0000000000000696
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发表时间：
2020-05-01
影响因子：
8.8
通讯作者：
Titulaer, Maarten J.
中科院分区：
文献类型：
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作者：
Munoz-Lopetegi, Amaia;de Bruijn, Marienke A. A. M.;Titulaer, Maarten J.
目的 谷氨酸脱羧酶 65（抗 GAD65）抗体与许多神经系统综合征相关。然而，它们的致病作用存在争议。我们的目的是描述抗 GAD65 患者的临床和临床旁特征并分析他们对免疫治疗的反应。方法 回顾性地，我们研究了抗 GAD65 阳性且有任何神经系统症状的患者 (n = 56)。我们使用 ELISA、免疫组织化学和基于细胞的测定法测试了血清和脑脊液。因此，我们通过 ELISA 将血清中的临界值设定为 10,000 IU/mL，将患者分为高浓度组 (n = 36) 和低浓度组 (n = 20)。我们比较了临床和免疫学特征并分析了对免疫治疗的反应。结果 34/36 名高浓度患者（94%）出现经典抗 GAD65 相关综合征：僵人综合征（7 例）、小脑性共济失调（3 例）、慢性癫痫（9 例）、边缘脑炎（9 例）或其中 2 种或更多前者重叠（6 例）。低浓度患者有广泛的、异质的症状谱。免疫疗法对 19/27 的治疗患者 (70%) 有效，但没有一个人完全康复。在可用的治疗前和治疗后样本中，15/17 名患者出现抗体浓度降低（中位降低 69%；范围 27%-99%），其中 14 例临床改善。 2名浓度不变的患者没有表现出临床改善。特定综合征之间没有观察到治疗反应存在差异。结论 大多数抗 GAD65 浓度较高（>10,000 IU/mL）的患者在免疫治疗后表现出一定程度的改善，但遗憾的是并未完全恢复。血清抗体浓度的变化可能有助于监测反应。对于抗 GAD65 浓度较低的患者，尤其是那些没有典型临床表型的患者，更有可能采用诊断替代方案。
Objective Antibodies against glutamic acid decarboxylase 65 (anti-GAD65) are associated with a number of neurologic syndromes. However, their pathogenic role is controversial. Our objective was to describe clinical and paraclinical characteristics of anti-GAD65 patients and analyze their response to immunotherapy. Methods Retrospectively, we studied patients (n = 56) with positive anti-GAD65 and any neurologic symptom. We tested serum and CSF with ELISA, immunohistochemistry, and cell-based assay. Accordingly, we set a cutoff value of 10,000 IU/mL in serum by ELISA to group patients into high-concentration (n = 36) and low-concentration (n = 20) groups. We compared clinical and immunologic features and analyzed response to immunotherapy. Results Classical anti-GAD65-associated syndromes were seen in 34/36 patients with high concentration (94%): stiff-person syndrome (7), cerebellar ataxia (3), chronic epilepsy (9), limbic encephalitis (9), or an overlap of 2 or more of the former (6). Patients with low concentrations had a broad, heterogeneous symptom spectrum. Immunotherapy was effective in 19/27 treated patients (70%), although none of them completely recovered. Antibody concentration reduction occurred in 15/17 patients with available pre- and post-treatment samples (median reduction 69%; range 27%-99%), of which 14 improved clinically. The 2 patients with unchanged concentrations showed no clinical improvement. No differences in treatment responses were observed between specific syndromes. Conclusion Most patients with high anti-GAD65 concentrations (>10,000 IU/mL) showed some improvement after immunotherapy, unfortunately without complete recovery. Serum antibody concentrations' course might be useful to monitor response. In patients with low anti-GAD65 concentrations, especially in those without typical clinical phenotypes, diagnostic alternatives are more likely.