Department of Neurology and Rehabilitation, Tampere University Hospital, Tampere, Finland.
Division 7, Tampere University Hospital, Tampere, Finland.
Orphanet J Rare Dis. 2018 Apr 10;13(1):55. doi: 10.1186/s13023-018-0787-5.
Autoantibodies against the smaller isoform of glutamate decarboxylase (GAD65Ab) reflect autoimmune etiologies in Type 1 diabetes (T1D) and several neurological disorders, including Stiff Person Syndrome (SPS). GAD65Ab are also reported in cases of epilepsy, indicating an autoimmune component. GAD65Ab in patients with co-occurring T1D, epilepsy or SPS may be part of either autoimmune pathogenesis. To dissect the etiologies associated with GAD65Ab, we analyzed GAD65Ab titer, epitope specificity and enzyme inhibition in GAD65Ab-positive patients diagnosed with epilepsy (n = 28), patients with epilepsy and T1D (n = 10), patients with SPS (n = 20), and patients with T1D (n = 42).
GAD65Ab epitope pattern in epilepsy differed from T1D and SPS patients. Four of 10 patients with co-occurring T1D and epilepsy showed GAD65Ab profiles similar to T1D patients, while lacking GAD65Ab characteristics found in GAD65Ab-positive epilepsy patients. One of these patients responded well to anti-epileptic drugs (AEDs), while another patient did not require medication for seizure control. The third patient was refractory due to a diagnosis of meningioma. The response of the remaining patient to AEDs was unknown. GAD65Ab in the remaining six patients with T1D and epilepsy showed profiles similar to those in epilepsy patients.
Different autoimmune responses associated with T1D, epilepsy and SPS are reflected by disease-specific GAD65Ab patterns. Moreover, the epileptic etiology in patients diagnosed with both T1D and epilepsy may present two different etiologies regarding their epileptic condition. In one group T1D co-occurs with non-autoimmune epilepsy. In the other group GAD65Ab are part of an autoimmune epileptic condition.
针对谷氨酸脱羧酶小同工型（GAD65Ab）的自身抗体反映了 1 型糖尿病（T1D）和包括僵人综合征（SPS）在内的几种神经疾病的自身免疫病因。GAD65Ab 也在癫痫病例中报告，表明存在自身免疫成分。同时患有 T1D、癫痫或 SPS 的患者的 GAD65Ab 可能是自身免疫发病机制的一部分。为了剖析与 GAD65Ab 相关的病因，我们分析了诊断为癫痫（n=28）、癫痫合并 T1D（n=10）、SPS（n=20）和 T1D（n=42）的 GAD65Ab 阳性患者的 GAD65Ab 滴度、表位特异性和酶抑制。
癫痫患者的 GAD65Ab 表位模式与 T1D 和 SPS 患者不同。10 名合并 T1D 和癫痫的患者中有 4 名表现出与 T1D 患者相似的 GAD65Ab 谱，而缺乏 GAD65Ab 阳性癫痫患者中发现的 GAD65Ab 特征。其中一名患者对抗癫痫药物（AEDs）反应良好，而另一名患者无需药物控制癫痫发作。第三位患者因诊断为脑膜瘤而难以治疗。其余患者对 AEDs 的反应情况未知。其余 6 名患有 T1D 和癫痫的患者的 GAD65Ab 表现出与癫痫患者相似的谱。
T1D、癫痫和 SPS 相关的不同自身免疫反应反映在疾病特异性的 GAD65Ab 模式中。此外，同时诊断为 T1D 和癫痫的患者的癫痫病因可能存在两种不同的癫痫发病机制。在一组中，T1D 与非自身免疫性癫痫并存。在另一组中，GAD65Ab 是自身免疫性癫痫的一部分。
