High prevalence of neuronal surface autoantibodies associated with cognitive deficits in cancer patients
High prevalence of neuronal surface autoantibodies associated with cognitive deficits in cancer patients
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DOI：
10.1007/s00415-017-8582-0
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发表时间：
2017-09-01
影响因子：
6
通讯作者：
Harms, Lutz
中科院分区：
文献类型：
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作者：
Finke, Carsten;Bartels, Frederik;Harms, Lutz
最近发现的神经元细胞表面抗体深刻地扩大了副肿瘤神经综合征的临床谱。这些综合征中的许多与认知功能受损有关，这是癌症患者日益关注的临床症状。然而，这些抗体在癌症患者中的频率及其与临床综合征的关系目前尚不清楚。在这里，我们调查了323例不同类型癌症患者和105例对照组中神经元细胞表面抗体和相关副肿瘤神经综合征的患病率。脑脊液和血清样本进行了分析的一个大面板的抗神经元抗体和所有患者进行了筛选认知缺陷。使用年龄标准化白蛋白脑脊液/血清比率评估血脑屏障完整性。在24.5%的癌症患者中观察到抗神经元自身抗体（与之相反，在没有癌症的神经系统对照患者中为3.1%，在健康对照中为2.5%），并且几乎完全在血清中检测到。大多数抗体针对细胞表面抗原（75.9%），最常见的伊加/IgM同种型靶向N-甲基-d-天冬氨酸（NMDA）受体。与抗体阴性患者相比，抗体阳性患者中认知缺陷和小脑综合征的发生率明显更高（21 vs. 7%，p = 2.7 x 10（-4）; 11 vs. 2%，p = 3.0 x 10（-3））。与具有其他神经功能缺损的抗体阳性患者相比，具有认知功能缺损的抗体阳性患者的脑脊液/血清白蛋白比值显著升高，表明血脑屏障功能障碍（49.1 x 10 - 3 vs. 12.0 x 10 - 3; p = 0.036）。我们的研究结果表明，抗神经元抗体在广泛的不同肿瘤类型中具有很高的患病率，并与不同的神经功能缺损相关。具体来说，结果表明，迄今为止尚未明确的认知副肿瘤综合征的患者与抗体靶向神经元表面抗原和并发血脑屏障功能障碍。因此，抗神经元抗体可能作为癌症患者中潜在治疗反应性认知障碍的生物标志物。
The recent discovery of neuronal cell-surface antibodies profoundly expanded the clinical spectrum of paraneoplastic neurological syndromes. Many of these syndromes are associated with impaired cognitive function, a clinical symptom that is of increasing concern in cancer patients. However, the frequency of these antibodies in cancer patients and their relation to clinical syndromes is currently unknown. Here, we investigated the prevalence of neuronal cell-surface antibodies and associated paraneoplastic neurological syndromes in 323 patients with different cancer types and in 105 controls. Cerebrospinal fluid and serum samples were analysed for a large panel of anti-neuronal antibodies and all patients were screened for cognitive deficits. Blood-brain barrier integrity was assessed using the age-normalized albumin cerebrospinal fluid/serum ratio. Anti-neuronal autoantibodies were observed in 24.5% of cancer patients (in contrast to 3.1% in neurological control patients without cancer and 2.5% in healthy controls) and were almost exclusively detected in serum. The majority of antibodies were directed against cell-surface antigens (75.9%), most frequently IgA/IgM isotypes targeting the N-methyl-d-aspartate (NMDA) receptor. Cognitive deficits and cerebellar syndromes were significantly more prevalent in antibody-positive in comparison with antibody-negative patients (21 vs. 7%, p = 2.7 x 10(-4); 11 vs. 2%, p = 3.0 x 10(-3)). Antibody-positive patients with cognitive deficits had a significantly increased albumin cerebrospinal fluid/serum ratio in comparison with antibody-positive patients with other neurological deficits, indicating blood-brain barrier dysfunction (49.1 x 10(-3) vs. 12.0 x 10(-3); p = 0.036). Our results show that anti-neuronal antibodies have a high prevalence in a wide range of different tumour types and are associated with distinct neurological deficits. Specifically, the results suggest a so far undefined cognitive paraneoplastic syndrome in patients with antibodies targeting neuronal surface antigens and concurrent blood-brain barrier dysfunction. Anti-neuronal antibodies might thus serve as a biomarker for potentially treatment-responsive cognitive impairments in cancer patients.