背景:已经在少数神经精神疾病病例中描述了针对钾电压门控通道亚家族A成员2(KCNA2)的自身抗体,但是它们的诊断和病理生理作用目前尚不清楚,给医疗实践带来挑战。
■我们回顾性收集了35例基于细胞和基于组织的检测中检测到的KCNA2IgG自身抗体患者的综合临床和临床数据。患者血清和脑脊液(CSF)用于表征抗原,临床血清学相关性,并测定IgG亚类。
结果:KCNA2自身抗体阳性患者(n=35,发病年龄中位数为65岁,16-83年的范围,74%的男性)主要表现为认知障碍和/或癫痫发作,但也表现为共济失调,步态障碍和人格改变。血清自身抗体属于IgG3和IgG1亚类,滴度范围为1:32至1:10,000。在8/21(38%)患者的CSF和4/96(4.2%)健康献血者的血清中发现了KCNA2IgG。KCNA2自身抗体与哺乳动物大脑的小脑和海马以及周围神经的近区区域的特征性解剖区域结合,但仅与细胞内表位反应。四名KCNA2自身抗体阳性患者的子集对免疫疗法有明显反应,同时转化为血清阴性,特别是那些表现出自身免疫性脑炎表型并接受早期免疫疗法的患者。可用的脑活检显示强烈的免疫细胞侵袭。KCNA2自身抗体与潜在肿瘤的相关性小于10%。
结论:我们的数据表明KCNA2自身免疫是临床异质性的。未来的研究应确定KCNA2自身抗体是直接致病还是次要发展。应考虑早期免疫疗法,特别是如果CSF中存在自身抗体,或者临床或诊断结果表明炎症正在进行.可疑的临床表型包括自身免疫性脑炎,非典型痴呆,新发癫痫和原因不明的癫痫发作。
Autoantibodies against the potassium voltage-gated channel subfamily A member 2 (KCNA2) have been described in a few cases of neuropsychiatric disorders, but their diagnostic and pathophysiological role is currently unknown, imposing challenges to medical practice.
We retrospectively collected comprehensive clinical and paraclinical data of 35 patients with KCNA2 IgG autoantibodies detected in cell-based and tissue-based assays. Patients\' sera and cerebrospinal fluid (CSF) were used for characterization of the antigen, clinical-serological correlations, and determination of IgG subclasses.
KCNA2 autoantibody-positive patients (n = 35, median age at disease onset of 65 years, range of 16-83 years, 74 % male) mostly presented with cognitive impairment and/or epileptic seizures but also ataxia, gait disorder and personality changes. Serum autoantibodies belonged to IgG3 and IgG1 subclasses and titers ranged from 1:32 to 1:10,000. KCNA2 IgG was found in the CSF of 8/21 (38 %) patients and in the serum of 4/96 (4.2 %) healthy blood donors. KCNA2 autoantibodies bound to characteristic anatomical areas in the cerebellum and hippocampus of mammalian brain and juxtaparanodal regions of peripheral nerves but reacted exclusively with intracellular epitopes. A subset of four KCNA2 autoantibody-positive patients responded markedly to immunotherapy alongside with conversion to seronegativity, in particular those presenting an autoimmune encephalitis phenotype and receiving early immunotherapy. An available brain biopsy showed strong immune cell invasion. KCNA2 autoantibodies occurred in less than 10 % in association with an underlying tumor.
Our data suggest that KCNA2 autoimmunity is clinically heterogeneous. Future studies should determine whether KCNA2 autoantibodies are directly pathogenic or develop secondarily. Early immunotherapy should be considered, in particular if autoantibodies occur in CSF or if clinical or diagnostic findings suggest ongoing inflammation. Suspicious clinical phenotypes include autoimmune encephalitis, atypical dementia, new-onset epilepsy and unexplained epileptic seizures.