Autoimmune limbic encephalitis in 39 patients: immunophenotypes and outcomes
Autoimmune limbic encephalitis in 39 patients: immunophenotypes and outcomes
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DOI：
10.1136/jnnp.2006.100644
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发表时间：
2007-04-01
影响因子：
11
通讯作者：
Dalmau, J.
中科院分区：
文献类型：
--
作者：
Bataller, L.;Kleopa, K. A.;Dalmau, J.
背景：大约40%的边缘系统脑炎患者没有可检测到的CNS抗体。目的：（1）确定在一个机构中临床上确定的边缘系统脑炎的谱，并将其与转诊进行抗体分析的患者进行比较。(2)将临床结果与自身抗原的细胞定位相关联。方法：前瞻性临床病例研究。免疫组化与大鼠脑，活海马神经元，HeLa细胞表达Kv钾通道和immunoblot.Results：在4年中，17例患者被确定在医院的宾夕法尼亚大学，费城，美国，22例患者的血清或CSF样本在其他地方诊断也进行了研究。我们的17名患者中有9名（53%）具有已知神经元抗原（副肿瘤或电压门控钾通道（VGKC））的抗体，5名（29%）具有通常在海马和小脑中表达的新型细胞膜抗原（nCMAg）的抗体。考虑到整个系列，39例患者中有19例（49%）具有已知抗原抗体，17例（44%）具有nCMAg抗体。35例患者获得随访（2-48个月，中位19个月）。与神经元内抗原抗体阳性患者相比，细胞膜抗原抗体阳性患者对治疗的反应有显著相关性（VGKC或nCMAg，p = 0.003）或nCMAg结论：（1）82%的边缘系统脑炎患者存在CNS抗体;（2）对治疗的反应性不限于VGKC抗体患者;（3）在许多患者中（29%来自单一机构），自身抗原未知，但发现在海马神经元细胞膜中高度富集;（4）这些抗体与良好的结局相关。
Background: About 40% of patients with limbic encephalitis do not have detectable CNS antibodies. Some of these patients have immune-mediated limbic encephalitis, but their frequency is unknown.Aims: (1) To determine the spectrum of limbic encephalitis identified on clinical grounds in a single institution, and compare it with that in patients referred for antibody analysis. (2) To correlate clinical outcomes with the cellular location of the autoantigens.Methods: Prospective clinical case studies. Immunohistochemistry with rat brain, live hippocampal neurones, HeLa cells expressing Kv potassium channels and immunoblot.Results: In 4 years, 17 patients were identified in the Hospital of the University of Pennsylvania, Philadelphia, USA, and the serum or CSF samples of 22 patients diagnosed elsewhere were also studied. 9 of our 17 (53%) patients had antibodies to known neuronal antigens (paraneoplastic or voltage gated potassium channels (VGKCs)) and 5 (29%) to novel cell-membrane antigens (nCMAg) typically expressed in the hippocampus and sometimes in the cerebellum. Considering the entire series, 19 of 39 (49%) patients had antibodies to known antigens, and 17 (44%) to nCMAg. Follow-up (2-48 months, median 19 months) was available for 35 patients. When compared with patients with antibodies to intraneuronal antigens, a significant association with response to treatment was found in those with antibodies to cell-membrane antigens in general (VGKC or nCMAg, p = 0.003) or to nCMAg (p = 0.006).Conclusions: (1) 82% of patients with limbic encephalitis prospectively identified on clinical grounds had CNS antibodies; (2) responsiveness to treatment is not limited to patients with VGKC antibodies; (3) in many patients (29% from a single institution), the autoantigens were unknown but were found to be highly enriched in neuronal cell membranes of the hippocampus; and (4) these antibodies are associated with a favourable outcome.