Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Italy.
Neuroimmunology Laboratory, IRCCS Mondino Foundation, Pavia, Italy.
Brain Behav Immun. 2021 Aug;96:106-112. doi: 10.1016/j.bbi.2021.05.017. Epub 2021 May 20.
Autoimmune encephalitis due to antibodies against neuronal surface antigens (NSA-Ab) frequently presents with cognitive impairment, often as the first and prevalent manifestation, but few studies have systematically assessed the frequency of NSA-Ab in consecutive patients with established neurodegenerative disorders.
We studied sera of 93 patients (41F, 52 M), aged 69.2 ± 9.4 years, with neurodegenerative conditions, and of 50 population controls aged over 60 years. Specific NSA-Abs were investigated by antigen-specific cell-based assays (CBAs). After testing, we evaluated the association between the NSA-Abs and clinical, CSF and radiological features.
The patients included 13/93 (13.8%) who had specific antibodies to neuronal surface antigens: 6 GlyR, 3 GABAR (1 also positive for AMPAR), 2 LGI1, 1 CASPR2 and 1 GABAR. One of the 50 controls (2%) was positive for NMDAR antibody and the others were negative on all tests (P = 0.020). No difference was observed in antibody frequency between patients presenting with parkinsonism and those presenting with dementia (P = 0.55); however, NSA-Ab were more frequent in those with unclassified forms of dementia (5/13, 38.5%) than in those with unclassified parkinsonism (2/9, 22.2%) or with classified forms of dementia (4/43, 9.3%) or parkinsonism (2/28, 7.1%) (P = 0.03). A logistic regression analysis demonstrated that an unclassified diagnosis (P = 0.02) and an irregular progression (P = 0.024) were predictors of seropositive status.
NSA-Abs are relatively frequent in patients with neurodegenerative disorders, particularly in those with an irregular disease progression of atypical clinical features, inconsistent with a recognized diagnosis. The significance of these antibodies and their possible primary or secondary roles need to be investigated in prospective studies.
由于神经元表面抗原（NSA-Ab）抗体引起的自身免疫性脑炎常表现为认知障碍，通常作为首发和常见表现，但很少有研究系统评估 NSA-Ab 在确诊的神经退行性疾病患者中的频率。
我们研究了 93 名（41 名女性，52 名男性）年龄为 69.2±9.4 岁的患有神经退行性疾病的患者的血清，以及 50 名年龄在 60 岁以上的人群对照。通过抗原特异性细胞基础测定法（CBAs）检测特异性 NSA-Abs。检测后，我们评估了 NSA-Abs 与临床、CSF 和影像学特征之间的关系。
患者中包括 13/93（13.8%）具有针对神经元表面抗原的特异性抗体：6 例甘氨酸受体（GlyR），3 例 GABAAR（1 例也对 AMPAR 呈阳性），2 例 LGI1，1 例 CASPR2 和 1 例 GABAAR。50 名对照中只有 1 名（2%）对 NMDAR 抗体呈阳性，其他人在所有检测中均为阴性（P=0.020）。在以帕金森病和痴呆起病的患者中，抗体的频率没有差异（P=0.55）；然而，在未分类的痴呆患者中，NSA-Ab 更为常见（13 例中有 5 例，38.5%），而未分类的帕金森病患者（9 例中有 2 例，22.2%）、分类的痴呆患者（43 例中有 4 例，9.3%）或帕金森病患者（28 例中有 2 例，7.1%）中相对较少（P=0.03）。逻辑回归分析表明，未分类的诊断（P=0.02）和不规则的疾病进展（P=0.024）是血清阳性状态的预测因素。
NSA-Ab 在神经退行性疾病患者中较为常见，尤其是在具有不典型临床表现和不规律疾病进展、不符合已确诊疾病的患者中。这些抗体的意义及其可能的原发性或继发性作用需要在前瞻性研究中进行研究。
