Neuronal autoantibodies

神经元自身抗体
  • 文章类型: Journal Article
    目的:我们以前证明白细胞介素-1受体介导的免疫激活有助于抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎的癫痫发作严重程度和记忆丧失。在本研究中,我们评估了髓样分化原发反应基因88(MyD88)的作用,Toll样受体信号中的衔接蛋白,抗NMDAR脑炎的关键表型特征。
    方法:通过渗透微型泵将单克隆抗NMDAR抗体或对照抗体注入MyD88敲除小鼠(MyD88-/-)和对照C56BL/6J小鼠(野生型[WT])的侧脑室2周。癫痫反应通过脑电图测量。输液完成后,电机,焦虑,并评估小鼠的记忆功能。使用免疫组织化学和定量实时聚合酶链反应确定与癫痫发作有关的主要炎症介质的星形胶质细胞(神经胶质原纤维酸性蛋白[GFAP])和小胶质细胞(离子化钙结合衔接分子1[Iba-1])激活和转录激活。分别。
    结果:如前所述,80%输注抗NMDAR抗体的WT小鼠(n=10)出现癫痫发作(中位数=11,四分位距[IQR]=2周内3-25)。相比之下,14只MyD88-/-小鼠中只有3只(21.4%)出现癫痫发作(0,IQR=0-.25,p=.01)。用抗体处理的WT小鼠在新的物体识别测试中也出现了记忆丧失,而在用抗NMDAR抗体(p=.03)或对照抗体(p=.04)治疗的MyD88-/-小鼠中,这种记忆缺陷并不明显。此外,与暴露于抗NMDAR抗体的WT小鼠相反,MyD88-/-小鼠对海马中趋化因子(C-C基序)配体2(CCL2)的诱导显着降低(p=.0001,Sidak测试)。在用抗NMDAR或对照抗体处理的MyD88-/-小鼠中,GFAP和Iba-1的表达没有显著变化。
    结论:这些研究结果表明,MyD88介导的信号传导有助于抗NMDAR脑炎的癫痫发作和记忆表型,CCL2激活可能参与这些特征的表达。MyD88炎症的去除可以是保护性和治疗相关的。
    OBJECTIVE: We previously demonstrated that interleukin-1 receptor-mediated immune activation contributes to seizure severity and memory loss in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. In the present study, we assessed the role of the myeloid differentiation primary response gene 88 (MyD88), an adaptor protein in Toll-like receptor signaling, in the key phenotypic characteristics of anti-NMDAR encephalitis.
    METHODS: Monoclonal anti-NMDAR antibodies or control antibodies were infused into the lateral ventricle of MyD88 knockout mice (MyD88-/-) and control C56BL/6J mice (wild type [WT]) via osmotic minipumps for 2 weeks. Seizure responses were measured by electroencephalography. Upon completion of the infusion, the motor, anxiety, and memory functions of the mice were assessed. Astrocytic (glial fibrillary acidic protein [GFAP]) and microglial (ionized calcium-binding adaptor molecule 1 [Iba-1]) activation and transcriptional activation for the principal inflammatory mediators involved in seizures were determined using immunohistochemistry and quantitative real-time polymerase chain reaction, respectively.
    RESULTS: As shown before, 80% of WT mice infused with anti-NMDAR antibodies (n = 10) developed seizures (median = 11, interquartile range [IQR] = 3-25 in 2 weeks). In contrast, only three of 14 MyD88-/- mice (21.4%) had seizures (0, IQR = 0-.25, p = .01). The WT mice treated with antibodies also developed memory loss in the novel object recognition test, whereas such memory deficits were not apparent in MyD88-/- mice treated with anti-NMDAR antibodies (p = .03) or control antibodies (p = .04). Furthermore, in contrast to the WT mice exposed to anti-NMDAR antibodies, the MyD88-/- mice had a significantly lower induction of chemokine (C-C motif) ligand 2 (CCL2) in the hippocampus (p = .0001, Sidak tests). There were no significant changes in the expression of GFAP and Iba-1 in the MyD88-/- mice treated with anti-NMDAR or control antibodies.
    CONCLUSIONS: These findings suggest that MyD88-mediated signaling contributes to the seizure and memory phenotype in anti-NMDAR encephalitis and that CCL2 activation may participate in the expression of these features. The removal of MyD88 inflammation may be protective and therapeutically relevant.
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  • 文章类型: Journal Article
    癌症免疫治疗的兴起已成为临床肿瘤学的一个里程碑。最重要的是,免疫检查点抑制剂治疗(ICI)与单克隆抗体靶向程序性细胞死亡蛋白1(PD-1),程序性细胞死亡配体1(PD-L1),和细胞毒性T淋巴细胞相关蛋白4(CTLA-4)提高了越来越多的恶性肿瘤的生存率。然而,尽管有临床益处,ICI相关的自身免疫已成为非复发相关的发病率和死亡率的重要原因。神经免疫相关不良事件(irAE-n)是特别严重的毒性,具有慢性疾病的高风险,长期依赖类固醇,并提前终止ICI治疗。虽然很好地描述了irAE-n的临床特征,对潜在的免疫机制和潜在的生物标志物知之甚少。最近,已经报道了irAE-n患者中神经元自身抗体的高频率,然而,其临床相关性尚不清楚.这里,我们提供了一个关于ICI治疗的有和没有irAE-n的癌症患者的神经元自身抗体谱的数据集,它的产生是为了研究神经元自身抗体在ICI诱导的自身免疫中的潜在作用。在2017年9月至2022年1月之间,29名接受irAE-n后ICI治疗的癌症患者的血清样本)和44名癌症对照患者,无高级别免疫相关不良事件(irAE,收集ICI治疗前后的n=44),并使用间接免疫荧光和免疫印迹测定法测试了一大批脑反应性和神经肌肉自身抗体。比较各组之间自身抗体的患病率,并与临床特征如结果和irAE-n表现相关。这些数据代表了ICI治疗的有和没有irAE-n的癌症患者之间神经元自身抗体谱的首次系统比较。为研究人员和临床医生提供有价值的信息。在未来,该数据集对于癌症患者神经元自身抗体患病率的荟萃分析可能是有价值的.
    The rise of cancer immunotherapy has been a milestone in clinical oncology. Above all, immune checkpoint inhibitor treatment (ICI) with monoclonal antibodies targeting programmed cell death protein 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) has improved survival rates for an increasing number of malignancies. However, despite the clinical benefits, ICI-related autoimmunity has become a significant cause of non-relapse-related morbidity and mortality. Neurological immune-related adverse events (irAE-n) are particularly severe toxicities with a high risk for chronic illness, long-term steroid dependency, and early ICI treatment termination. While the clinical characteristics of irAE-n are well described, little is known about underlying immune mechanisms and potential biomarkers. Recently, high frequencies of neuronal autoantibodies in patients with irAE-n have been reported, however, their clinical relevance is unclear. Here, we present a dataset on neuronal autoantibody profiles in ICI-treated cancer patients with and without irAE-n, which was generated to investigate the potential role of neuronal autoantibodies in ICI-induced autoimmunity. Between September 2017 and January 2022 serum samples of 29 cancer patients with irAE-n post-ICI treatment) and 44 cancer control patients without high-grade immune-related adverse events (irAEs, n = 44 pre- and post-ICI treatment) were collected and tested for a large panel of brain-reactive and neuromuscular autoantibodies using indirect immunofluorescence and immunoblot assays. Prevalence of autoantibodies was compared between the groups and correlated with clinical characteristics such as outcome and irAE-n manifestation. These data represent the first systematic comparison of neuronal autoantibody profiles between ICI-treated cancer patients with and without irAE-n, providing valuable information for both researchers and clinicians. In the future, this dataset may be valuable for meta-analyses on the prevalence of neuronal autoantibodies in cancer patients.
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  • 文章类型: Journal Article
    抗GAD65自身抗体(GAD65-Abs)可能发生在癫痫和其他神经系统疾病的患者中,但临床意义尚不明确。尽管高水平的GAD65-Ab被认为在神经精神疾病中具有致病性,低或中等水平只被认为是纯粹的旁观者,例如,1型糖尿病(DM1)。在这种情况下,尚未明确评估基于细胞的测定(CBA)和免疫组织化学(IHC)对GAD65-Ab检测的价值。
    为了重新评估高水平的GAD65-Ab与神经精神疾病有关而低水平仅与DM1有关的假设,并将ELISA结果与CBA和IHC进行比较以确定这些测试的附加价值。
    研究了先前在常规临床实践中通过ELISA评估的GAD65-Ab的111份血清。测试的临床适应症是,例如,疑似自身免疫性脑炎或癫痫(神经精神队列;n=71,7例最初通过ELISA检测GAD65-Abs呈阳性),和DM1或成人隐匿性自身免疫性糖尿病(DM1/LADA队列(n=40,最初全部检测为阳性))。通过ELISA重新检测血清中的GAD65-Abs,CBA,IHC。此外,我们通过CBA检查了GAD67-Abs的可能存在,通过IHC检查了其他神经元自身抗体的可能存在.通过选择的CBA进一步测试显示不同于GAD65的IHC模式的样品。
    ELISA重新测试神经精神疾病患者的GAD65-Abs水平高于DM1/LADA患者(仅比较了重新测试的阳性样品;6vs.38;中位数47,092U/mL与581U/mL;p=0.02)。只有当抗体水平高于10,000U/mL时,GAD-Ab通过CBA和IHC均显示阳性,研究队列之间的患病率没有差异。我们在一名癫痫患者中发现了其他神经元抗体(mGluR1-Abs,GAD-Abs阴性),在脑炎患者中,还有两名LADA患者.
    神经精神疾病患者的GAD65-Abs水平明显高于DM1/LADA患者,然而,CBA和IHC阳性仅与高水平的GAD65-Abs相关,而不是潜在的疾病。
    UNASSIGNED: Anti-GAD65 autoantibodies (GAD65-Abs) may occur in patients with epilepsy and other neurological disorders, but the clinical significance is not clear-cut. Whereas high levels of GAD65-Abs are considered pathogenic in neuropsychiatric disorders, low or moderate levels are only considered as mere bystanders in, e.g., diabetes mellitus type 1 (DM1). The value of cell-based assays (CBA) and immunohistochemistry (IHC) for GAD65-Abs detection has not been clearly evaluated in this context.
    UNASSIGNED: To re-evaluate the assumption that high levels of GAD65-Abs are related to neuropsychiatric disorders and lower levels only to DM1 and to compare ELISA results with CBA and IHC to determine the additional value of these tests.
    UNASSIGNED: 111 sera previously assessed for GAD65-Abs by ELISA in routine clinical practice were studied. Clinical indications for testing were, e.g., suspected autoimmune encephalitis or epilepsy (neuropsychiatric cohort; n = 71, 7 cases were initially tested positive for GAD65-Abs by ELISA), and DM1 or latent autoimmune diabetes in adults (DM1/LADA cohort (n = 40, all were initially tested positive)). Sera were re-tested for GAD65-Abs by ELISA, CBA, and IHC. Also, we examined the possible presence of GAD67-Abs by CBA and of other neuronal autoantibodies by IHC. Samples that showed IHC patterns different from GAD65 were further tested by selected CBAs.
    UNASSIGNED: ELISA retested GAD65-Abs level in patients with neuropsychiatric diseases was higher than in patients with DM1/LADA (only retested positive samples were compared; 6 vs. 38; median 47,092 U/mL vs. 581 U/mL; p = 0.02). GAD-Abs showed positive both by CBA and IHC only if antibody levels were above 10,000 U/mL, without a difference in prevalence between the studied cohorts. We found other neuronal antibodies in one patient with epilepsy (mGluR1-Abs, GAD-Abs negative), and in a patient with encephalitis, and two patients with LADA.
    UNASSIGNED: GAD65-Abs levels are significantly higher in patients with neuropsychiatric disease than in patients with DM1/LADA, however, positivity in CBA and IHC only correlates with high levels of GAD65-Abs, and not with the underlying diseases.
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  • 文章类型: Journal Article
    未经证实:神经免疫相关不良事件(irAE-n)是免疫检查点抑制剂(ICI)的严重和潜在致命毒性。迄今为止,神经元自身抗体在irAE-n中的临床意义尚不清楚.这里,我们表征了irAE-n患者的神经元自身抗体谱,并将其与ICI治疗的无irAE-n的癌症患者进行了比较.
    未经证实:在本队列研究(DRKS00012668)中,我们连续收集了29例患有irAE-n的癌症患者(n=2pre-ICI,n=29post-ICI)和44例未患有irAE-n的癌症对照患者(n=44在ICI前后)的临床数据和血清样本.使用间接免疫荧光和免疫印迹分析,对血清样本进行了大量神经肌肉和脑反应性自身抗体的检测.
    未经批准:IrAE-n患者和对照组接受了针对程序性死亡蛋白(PD-)1(61%和62%)的ICI治疗,程序性死亡配体(PD-L)1(18%和33%)或PD-1和细胞毒性T淋巴细胞相关蛋白(CTLA-)4(21%和5%)。最常见的恶性肿瘤是黑色素瘤(55%)和肺癌(11%和14%)。IrAE-n影响周围神经系统(59%),中枢神经系统(21%),或两者(21%)。在irAE-n患者中,神经肌肉自身抗体的患病率为63%,与ICI治疗的没有irAE-n的癌症患者相比更高(7%,p<.0001)。靶向表面的脑反应性自身抗体(抗GABABR,-NMDAR,-髓鞘),细胞内(抗GFAP,-Zic4,-隔膜复合物),在13例irAE-n患者(45%)中检测到未知抗原。相比之下,44例对照中只有9例(20%)在ICI给药前出现脑反应性自身抗体.然而,七个对照在ICI启动后发展了从头脑反应性自身抗体,因此,有和没有irAE-n的ICI治疗患者的脑反应性自身抗体患病率相当(p=.36).虽然特异性脑反应性自身抗体与临床表现之间没有明确的关联,存在至少一种选择的神经肌肉自身抗体(抗滴度,抗骨骼肌,抗心肌,抗LRP4,抗RyR,抗AchR)对诊断肌炎的敏感性为80%(95%CI0.52-0.96),特异性为88%(95%CI0.76-0.95),心肌炎,或者重症肌无力.
    未经证实:神经肌肉自身抗体可作为诊断和潜在预测危及生命的ICI诱导的神经肌肉疾病的可行标志物。然而,脑反应性自身抗体在ICI治疗的有和没有irAE-n的患者中都很常见,因此,其致病意义仍不清楚。
    Neurological immune-related adverse events (irAE-n) are severe and potentially fatal toxicities of immune checkpoint inhibitors (ICI). To date, the clinical significance of neuronal autoantibodies in irAE-n is poorly understood. Here, we characterize neuronal autoantibody profiles in patients with irAE-n and compare these with ICI-treated cancer patients without irAE-n.
    In this cohort study (DRKS00012668), we consecutively collected clinical data and serum samples of 29 cancer patients with irAE-n (n = 2 pre-ICI, n = 29 post-ICI) and 44 cancer control patients without irAE-n (n = 44 pre- and post-ICI). Using indirect immunofluorescence and immunoblot assays, serum samples were tested for a large panel of neuromuscular and brain-reactive autoantibodies.
    IrAE-n patients and controls received ICI treatment targeting programmed death protein (PD-)1 (61% and 62%), programmed death ligand (PD-L)1 (18% and 33%) or PD-1 and cytotoxic T-lymphocyte-associated protein (CTLA-)4 (21% and 5%). Most common malignancies were melanoma (both 55%) and lung cancer (11% and 14%). IrAE-n affected the peripheral nervous system (59%), the central nervous system (21%), or both (21%). Prevalence of neuromuscular autoantibodies was 63% in irAE-n patients, which was higher compared to ICI-treated cancer patients without irAE-n (7%, p <.0001). Brain-reactive autoantibodies targeting surface (anti-GABABR, -NMDAR, -myelin), intracellular (anti-GFAP, -Zic4, -septin complex), or unknown antigens were detected in 13 irAE-n patients (45%). In contrast, only 9 of 44 controls (20%) presented brain-reactive autoantibodies before ICI administration. However, seven controls developed de novo brain-reactive autoantibodies after ICI initiation, therefore, prevalence of brain-reactive autoantibodies was comparable between ICI-treated patients with and without irAE-n (p = .36). While there was no clear association between specific brain-reactive autoantibodies and clinical presentation, presence of at least one of six selected neuromuscular autoantibodies (anti-titin, anti-skeletal muscle, anti-heart muscle, anti-LRP4, anti-RyR, anti-AchR) had a sensitivity of 80% (95% CI 0.52-0.96) and a specificity of 88% (95% CI 0.76-0.95) for the diagnosis of myositis, myocarditis, or myasthenia gravis.
    Neuromuscular autoantibodies may serve as a feasible marker to diagnose and potentially predict life-threatening ICI-induced neuromuscular disease. However, brain-reactive autoantibodies are common in both ICI-treated patients with and without irAE-n, hence, their pathogenic significance remains unclear.
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  • 文章类型: Journal Article
    城市生活可能导致患精神疾病的风险更高,但是迄今为止,没有证据表明城市环境与精神疾病中神经自身抗体的发生之间存在任何相关性。我们的目标是确定生活在不同的农村和城市环境中的有和没有神经自身抗体的患者数量是否不同。
    我们通过横断面设计从哥廷根精神病学和心理治疗大学医学中心招募了167名精神病患者,并测定了他们的血清和/或CSF神经自身抗体。病人住在德国下萨克森州,图林根,还有Hessen.他们的数据是结合他们的主要居住地进行调查的。根据他们的主要居住地,我们将他们分为五个不同的类别:一个农村环境和四个不同的城市环境,这取决于他们的人口数量。
    我们确定了36名患有神经自身抗体的精神病患者,和131名精神病患者没有。总的来说,24名患有神经自身抗体的精神病患者被归类为共享可能,可能,或者根据我们最近设定的标准确定的自身免疫起源。我们观察到一个不显着的趋势,即有神经自身抗体和可能或确定的自身免疫起源的精神病患者(45.8%)生活在人口超过100,000的主要城市中,而没有出现自身抗体证据的精神病患者(26.4%)。然而,我们发现(1)有和没有神经自身抗体的精神病患者之间或(2)精神病患者之间没有相关差异,可能,或确定的自身免疫起源,以及与不同的农村和城市环境相关的没有这种自身抗体的人。
    农村和城市环境固有的不同方面似乎与确定下萨克森州精神病患者中神经自身抗体的发生频率无关,图林根,和德国的黑森州。此外,应进行涉及德国其他州的大规模研究,以排除任何地区差异,并研究大城市自身免疫介导的精神病综合征发生频率较高的趋势.
    UNASSIGNED: City living might lead to a higher risk of psychiatric disease, but to date there is no evidence of any correlation between an urban environment and the occurrence of neural autoantibodies in psychiatric disease. Our aim is to identify whether the number of patients with and without neural autoantibodies living in diverse rural and urban environments differ.
    UNASSIGNED: We enrolled retrospectively a cohort of 167 psychiatric patients via a cross-sectional design from the Department of Psychiatry and Psychotherapy University Medical Center Göttingen and determined serum and/or CSF neural autoantibodies in them. The patients live in the German states of Lower Saxony, Thuringia, and Hessen. Their data were investigated in conjunction with the location of their primary residence. We categorized them into five different categories depending upon their primary residence: one rural and four different urban environments depending on their population numbers.
    UNASSIGNED: We identified 36 psychiatric patients with neural autoantibodies, and 131 psychiatric patients with none. In total, 24 psychiatric patients with neural autoantibodies were classified as sharing a possible, probable, or definitive autoimmune origin according to our recently set criteria. We observed as a non-significant trend that more psychiatric patients with neural autoantibodies and a probable or definitive autoimmune origin (45.8%) live in a major city with over 100,000 inhabitants than do psychiatric patients presenting no evidence of autoantibodies (26.4%). However, we identified no relevant differences between (1) psychiatric patients with and without neural autoantibodies or between (2) psychiatric patients with a possible, probable, or definitive autoimmune origin and those without such autoantibodies in relation to the diverse rural and urban environmental settings.
    UNASSIGNED: The inherently different aspects of rural and urban environments do not appear to be relevant in determining the frequency of neural autoantibodies in psychiatric patients in Lower Saxony, Thuringia, and Hessen in Germany. Furthermore, large-scale studies involving other states across Germany should be conducted to exclude any regional differences and to examine the tendency of a higher frequency in large cities of autoimmune-mediated psychiatric syndromes.
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  • 文章类型: Journal Article
    未经证实:与精神病综合征相关的抗神经自身抗体在精神病学中是一种日益增多的现象。我们的研究旨在评估混合精神病患者队列中与不同精神病综合征相关的神经自身抗体的频率和类型。
    UNASSIGNED:我们从精神病学和心理治疗部门回顾性地招募了167名患者,哥廷根大学医学中心进行这项研究。临床特征,包括通过《精神病学精神病理学评估和文献手册》(AMDP)对精神病理学进行评估,神经系统检查,脑脊液(CSF),对患者进行磁共振成像(MRI)和脑电图(EEG)分析。出于鉴别诊断原因,在所有患者中测量血清和/或CSF抗神经自身抗体。
    未经授权:我们将患者分为三组:(1)患有CSF和/或血清自身抗体的精神病患者[PSYCH-AB,n=25(14.9%)],(2)精神病患者CSF自身抗体[PSYCH-ABCSF+,n=13(7.8%)]和(3)那些血清和/或CSF中没有自身抗体的精神病患者[PSYCH-AB-,n=131]。血清神经自身抗体的患病率为14.9%(PSYCH-AB+),而在我们的精神病队列中,7.2%的患者有CSF自身抗体(PSYCH-ABCSF+).在呈现神经自身抗体(PSYCH-AB和PSYCH-ABCSF)的患者中,最普遍的精神病诊断是神经认知障碍(61-67%)和情绪障碍(25-36%)。然而,精神病诊断,神经功能缺损,和脑脊液的实验室结果,三组之间的EEG或MRI没有差异。为了评估神经自身抗体结果的相关性,我们应用了最近的标准,可能,在典型的谵妄患者和PSYCH-AB+队列中,或确定的基于自身免疫的精神病综合征。适用于任何基于自身免疫的精神病综合征的标准,我们在167例患者中的13例(7.8%)发现了可能的基于自身免疫的精神病综合征,在167例患者中的11例(6.6%)发现了明确的基于自身免疫的精神病综合征.
    UNASSIGNED:在我们的精神病队列中,主要在出现神经认知和情绪障碍的患者中检测到神经自身抗体。精神病综合征与神经自身抗体的表型表现与没有神经自身抗体的表型表现没有差异。因此,有必要进行更多的研究来优化生物标志物研究,以帮助临床医生在谵妄状态下需要快速临床反应时区分具有潜在神经自身抗体的患者。
    UNASSIGNED: Anti-neural autoantibodies associated with psychiatric syndromes is an increasing phenomenon in psychiatry. Our investigation aimed to assess the frequency and type of neural autoantibodies associated with distinct psychiatric syndromes in a mixed cohort of psychiatric patients.
    UNASSIGNED: We recruited 167 patients retrospectively from the Department of Psychiatry and Psychotherapy, University Medical Center Göttingen for this study. Clinical features including the assessment of psychopathology via the Manual for Assessment and Documentation of Psychopathology in Psychiatry (AMDP), neurological examination, cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) and electroencephalography (EEG) analysis were done in patients. Serum and or CSF anti- neural autoantibodies were measured in all patients for differential diagnostic reasons.
    UNASSIGNED: We divided patients in three different groups: (1) psychiatric patients with CSF and/or serum autoantibodies [PSYCH-AB+, n = 25 (14.9%)], (2) psychiatric patients with CSF autoantibodies [PSYCH-AB CSF+, n = 13 (7.8%)] and (3) those psychiatric patients without autoantibodies in serum and/or CSF [PSYCH-AB-, n = 131]. The prevalence of serum neural autoantibodies was 14.9% (PSYCH-AB+), whereas 7.2% had CSF autoantibodies (PSYCH-AB CSF+) in our psychiatric cohort. The most prevalent psychiatric diagnoses were neurocognitive disorders (61-67%) and mood disorders (25-36%) in the patients presenting neural autoantibodies (PSYCH-AB+ and PSYCH-AB CSF+). However, psychiatric diagnoses, neurological deficits, and laboratory results from CSF, EEG or MRI did not differ between the three groups. To evaluate the relevance of neural autoantibody findings, we applied recent criteria for possible, probable, or definitive autoimmune based psychiatric syndromes in an paradigmatic patient with delirium and in the PSYCH-AB+ cohort. Applying criteria for any autoimmune-based psychiatric syndromes, we detected a probable autoimmune-based psychiatric syndrome in 13 of 167 patients (7.8%) and a definitive autoimmune-based psychiatric syndrome in 11 of 167 patients (6.6%).
    UNASSIGNED: Neural autoantibodies were detected mainly in patients presenting neurocognitive and mood disorders in our psychiatric cohort. The phenotypical appearance of psychiatric syndromes in conjunction with neural autoantibodies did not differ from those without neural autoantibodies. More research is therefore warranted to optimize biomarker research to help clinicians differentiate patients with potential neural autoantibodies when a rapid clinical response is required as in delirium states.
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  • 文章类型: Journal Article
    Objective: The objective of the study was to determine the incidence of antibodies against neuronal surface antigens (NSA-ab) in patients with different types of epilepsy, in comparison with the subjects diagnosed with immune-mediated disorders. Methods: Forty patients with drug-resistant epilepsy (DRE) of unknown origin, 16 with post-stroke epilepsy, and 23 with systemic autoimmune disorders (SAD) with CNS involvement were included. NSA-ab were sought in serum using indirect immunofluorescence method. Relationships were analyzed between presence of NSA-ab and clinical presentation. Results: NSA-ab was detected in the sera from five patients: anti-DPPX in one patient, anti-AMPAR1/R2 in two, anti-LGI1 in one and, in one case, both anti-CASPR2 and DPPX IgG. Out of these five patients, three represented the SAD subgroup and two the DRE subgroup. None of the patients with post-stroke epilepsy was positive for NSA-ab. Significance: Autoimmune etiology is worth considering in patients with drug-resistant epilepsy of unknown origin. The presence of NSA-ab in patients with systemic autoimmune disorders may be caused by unspecifically enhanced autoimmune reactivity. NSA-ab seem not to be related to epilepsy resulting from ischemic brain injury.
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  • 文章类型: Journal Article
    抗N-甲基-D-天冬氨酸(NMDA)受体脑炎表现为认知功能急剧下降,异常运动,和严重的癫痫发作,这可能是具有挑战性的控制与传统的抗癫痫药物。我们以前证明了脑室内(i.c.v.)从受影响的患者的脑脊液给药,或纯化的NMDA受体抗体从脑炎患者到小鼠沉淀性癫痫发作,从而证实抗体是癫痫发作的直接致病性。尽管不同的抗NMDA受体抗体库可能导致脑炎患者的不同临床表现,特异性抗体在癫痫发作表达中的作用,电机,和认知表型仍不清楚。使用三种不同的患者来源的单克隆抗体,在NMDA受体的N端结构域(NTD)内具有不同的表位,我们描述了癫痫发作的负担,小鼠的运动活动和焦虑相关行为。我们发现连续给予5F5,2G6或3C11抗体2周导致癫痫发作,使用皮质螺钉电极进行连续脑电图测量。所有三个抗体治疗组的癫痫发作负担相当。在抗体输注停止后3天,癫痫发作伴随海马C-C趋化因子配体2(CCL2)mRNA表达增加。抗体不影响小鼠的运动表现或焦虑评分。这些发现表明靶向NMDA受体内不同表位的神经元抗体可能导致类似的癫痫发作表型。
    Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis manifests with precipitous cognitive decline, abnormal movements, and severe seizures that can be challenging to control with conventional anti-seizure medications. We previously demonstrated that intracerebroventricular (i.c.v.) administration of cerebrospinal fluid from affected patients, or purified NMDA receptor antibodies from encephalitis patients to mice precipitated seizures, thereby confirming that antibodies are directly pathogenic for seizures. Although different repertoires of anti-NMDA receptor antibodies could contribute to the distinct clinical manifestations in encephalitis patients, the role of specific antibodies in the expression of seizure, motor, and cognitive phenotypes remains unclear. Using three different patient-derived monoclonal antibodies with distinct epitopes within the N-terminal domain (NTD) of the NMDA receptor, we characterized the seizure burden, motor activity and anxiety-related behavior in mice. We found that continuous administration of 5F5, 2G6 or 3C11 antibodies for 2 weeks precipitated seizures, as measured with continuous EEG using cortical screw electrodes. The seizure burden was comparable in all three antibody-treated groups. The seizures were accompanied by increased hippocampal C-C chemokine ligand 2 (CCL2) mRNA expression 3 days after antibody infusion had stopped. Antibodies did not affect the motor performance or anxiety scores in mice. These findings suggest that neuronal antibodies targeting different epitopes within the NMDA receptor may result in a similar seizure phenotype.
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  • 文章类型: Journal Article
    暂无摘要。
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  • 文章类型: Journal Article
    In recent years, as an increasing number of neuronal autoantibodies have been detected and used for clinical diagnosis, clinicians have become more aware of autoimmune encephalitis, causing its reported incidence to trend upward over several years. To date, however, there has been no large-scale epidemiological survey of autoimmune encephalitis in adults and children, and its epidemiological characteristics remain unclear. Six main types of antibodies are detected and used to diagnose autoimmune encephalitis in Chongqing, Southwestern China: anti-NMDA receptor antibody, anti-GABAB receptor antibody, anti-LGI1 antibody, anti-CASPR2 antibody, anti-AMPA1 receptor antibody, and anti-AMPA2 receptor antibody. From January 2012 to February 2018, 189 patients at six general hospitals in Chongqing were diagnosed with autoimmune encephalitis and were positive for neuronal autoantibodies. In this report, the epidemic situation and the antibody distribution among these patients are analyzed and described in detail. The differences in disease severity among different ages and between the sexes are evaluated, and the correlation between antibody titer and disease severity is also assessed.
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