CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
Front Immunol. 2024 Jan 25;14:1289175. doi: 10.3389/fimmu.2023.1289175. eCollection 2023.
Autoantibodies are useful biomarkers for the early detection and diagnosis of autoimmune cerebellar ataxia (ACA).
To identify novel autoantibody candidates in ACA patients.
Patients with cerebellar ataxia of unknown cause were recruited from July 2018 to February 2023. Anti-neural autoantibodies in patient samples were detected by tissue-based indirect immunofluorescence assay (TBA) on rat cerebellum sections. TBA-positive samples were further screened for well-established anti-neural autoantibodies using commercial kits. Tissue-immunoprecipitation (TIP) and subsequent mass spectrometric (MS) analysis were used to explore the target antigens of autoantibodies in samples that were TBA-positive but negative for known autoantibodies. The specific binding between autoantibodies and the identified target antigen was confirmed by neutralization experiments, recombinant cell-based indirect immunofluorescence assay (CBA), and western blotting experiments.
The eukaryotic translation elongation factor 1 delta (EEF1D) protein was identified as a target antigen of autoantibodies in samples from a 43-year-old female ACA patient, while the specific binding of autoantibodies and EEF1D was confirmed by subsequent experiments. A second anti-EEF1D autoantibody-positive ACA patient, a 59-year-old female, was detected in simultaneous screening. The main clinical manifestations in each of the two patients were cerebellar syndrome, such as unsteady walking and limb ataxia. Both patients received immunotherapy, including corticosteroids, intravenous immunoglobulin, and mycophenolate mofetil. Their outcomes provided evidence to support the effectiveness of immunotherapy, but the cerebellar atrophy that occurred before treatment may be irreversible.
In the current study, we identified anti-EEF1D autoantibody as a novel autoantibody candidate in ACA. Its pathological roles and diagnostic value need to be further verified in larger-scale studies.
自身抗体是早期发现和诊断自身免疫性小脑性共济失调（ACA）的有用生物标志物。
鉴定 ACA 患者中的新型自身抗体候选物。
从 2018 年 7 月至 2023 年 2 月，招募原因不明的小脑性共济失调患者。使用大鼠小脑切片的基于组织的间接免疫荧光测定（TBA）检测患者样本中的抗神经自身抗体。使用商业试剂盒对 TBA 阳性样本进行进一步筛选，以检测已知的抗神经自身抗体。组织免疫沉淀（TIP）和随后的质谱（MS）分析用于探索 TBA 阳性但缺乏已知自身抗体的样本中自身抗体的靶抗原。通过中和实验、重组细胞间接免疫荧光测定（CBA）和 Western blot 实验验证自身抗体与鉴定的靶抗原之间的特异性结合。
鉴定出真核翻译延伸因子 1 德尔塔（EEF1D）蛋白为来自 43 岁女性 ACA 患者样本中自身抗体的靶抗原，随后的实验证实了自身抗体与 EEF1D 的特异性结合。同时筛查还检测到第二位抗 EEF1D 自身抗体阳性 ACA 患者，为 59 岁女性。两名患者均接受了免疫治疗，包括皮质类固醇、静脉注射免疫球蛋白和霉酚酸酯。每位患者的主要临床表现均为小脑综合征，如行走不稳和肢体共济失调。两项研究结果均表明免疫治疗有效，但治疗前发生的小脑萎缩可能是不可逆的。
在本研究中，我们鉴定出抗 EEF1D 自身抗体为 ACA 中的一种新型自身抗体候选物。其病理作用和诊断价值需要在更大规模的研究中进一步验证。
