Section for Translational Epilepsy Research, Dept. of Neuropathology, University Hospital Bonn, Bonn, Germany.
Dept. of Epileptology, University Hospital Bonn, Bonn, Germany.
PLoS One. 2020 Oct 29;15(10):e0241289. doi: 10.1371/journal.pone.0241289. eCollection 2020.
Temporal lobe adult-onset seizures (TAOS) related to autoimmunity represent an increasingly recognized disease syndrome within the spectrum of epilepsies. In this context, certain autoantibodies (autoABs) were often associated with limbic encephalitis (LE). Here, we aimed to gain insights into (a) the distribution of 'neurological' autoABs (neuroABs, defined as autoABs targeting neuronal surface structures or 'onconeuronal' ABs or anti-glutamate acid decarboxylase 65 (GAD65) autoABs) in a large consecutive TAOS patient cohort, to characterize (b) clinical profiles of seropositive versus seronegative individuals and to find (c) potential evidence for other autoABs. Blood sera/cerebrospinal fluid (CSF) of TAOS patients (n = 800) and healthy donors (n = 27) were analyzed for neuroABs and screened for other autoABs by indirect immunofluorescence on hippocampal/cerebellar sections and immunoblots of whole brain and synaptosome lysates. Serological results were correlated with clinico-neuropsychological features. 13% of TAOS patients (n = 105) were neuroAB+, with anti-GAD65 and anti-N-methyl-D-aspartate receptors (NMDAR) as most frequent autoABs in this group. In our screening tests 25% of neuroAB- patients (n = 199) were positive (screening+), whereas all control samples were negative (n = 27). Intriguingly, key clinico-neuropsychological characteristics including magnetic resonance imaging (MRI) findings, epileptiform electroencephalographic (EEG) activity, and inflammatory cellular infiltrates in CSF were shared to a greater extent by neuroAB+ with neuroAB-/screening+ patients than with neuroAB-/screening- patients. Serological testing in a large consecutive TAOS patient series revealed seropositivity for anti-GAD65 autoABs as the most frequent neuroAB. Intriguingly, neuroAB+ individuals were virtually indistinguishable from neuroAB-/screening+ patients in several major clinical features. In contrast, neuroAB-/screening- TAOS patients differed in many parameters. These data support the potential presence of so far unrecognized autoABs in patients with TAOS.
颞叶成人发作性癫痫（TAOS）与自身免疫有关，是癫痫谱中一种越来越被认可的疾病综合征。在这种情况下，某些自身抗体（autoABs）通常与边缘性脑炎（LE）相关。在此，我们旨在深入了解：（a）在一个大的连续 TAOS 患者队列中，“神经”自身抗体（neuroABs，定义为针对神经元表面结构的自身抗体或“神经原性”ABs 或抗谷氨酸脱羧酶 65（GAD65）自身抗体）的分布；（b）血清阳性与血清阴性个体的临床特征；并寻找（c）其他自身抗体的潜在证据。TAOS 患者（n=800）和健康供体（n=27）的血清/脑脊液（CSF）通过在海马/小脑切片上进行间接免疫荧光和全脑和突触体裂解物的免疫印迹分析，检测 neuroABs，并筛选其他自身抗体。血清学结果与临床神经心理学特征相关。13%的 TAOS 患者（n=105）为 neuroAB+，其中抗 GAD65 和抗 N-甲基-D-天冬氨酸受体（NMDAR）是该组中最常见的自身抗体。在我们的筛选试验中，25%的 neuroAB-患者（n=199）呈阳性（筛选+），而所有对照样本均为阴性（n=27）。有趣的是，磁共振成像（MRI）发现、癫痫样脑电图（EEG）活动和 CSF 中的炎症细胞浸润等关键临床神经心理学特征在 neuroAB+患者中与 neuroAB-/筛选+患者的共享程度高于与 neuroAB-/筛选-患者。在一个大的连续 TAOS 患者系列中进行的血清学检测显示，抗 GAD65 自身抗体的血清阳性率为最常见的 neuroAB。有趣的是，在许多主要临床特征方面，neuroAB+个体与 neuroAB-/筛选+患者几乎无法区分。相比之下，neuroAB-/筛选-的 TAOS 患者在许多参数上存在差异。这些数据支持 TAOS 患者中存在尚未被识别的自身抗体的可能性。
