Yeo T, Chen Z, Chai J Y H, Tan K
Department of Neurology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore.
Department of Neurology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore; Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
J Neurol Sci. 2017 Jul 15;378:85-90. doi: 10.1016/j.jns.2017.04.045. Epub 2017 Apr 28.
The presence of VGKC-complex antibodies, without LGI1/CASPR2 antibodies, as a standalone marker for neurological autoimmunity remains controversial. Additionally, the lack of an unequivocal VGKC-complex antibody cut-off level defining neurological autoimmunity makes it important to test for monospecific antibodies. We aim to determine the performance characteristics of a commercial assay (Euroimmun, Lübeck, Germany) for LGI1/CASPR2 antibody detection in patients with very high VGKC-complex antibody levels and report their clinico-serological associations.
We identified 8 patients in our cohort with the highest VGKC-complex antibody levels (median 2663.5pM, range 933-6730pM) with VGKC-complex antibody related syndromes (Group A). Two other groups were identified; 1 group with suspected neuronal surface antibody syndromes and negative for VGKC-complex antibodies (Group B, n=8), and another group with cerebellar ataxia and negative for onconeuronal antibodies (Group C, n=8).
Seven out of 8 patients (87.5%) in Group A had LGI1 and/or CASPR2 antibodies. One Group B patient had LGI1 antibodies but was negative on re-testing with a live cell assay. No Group C patients had monospecific antibodies. Inter-rater reliability was high; combining Groups A and B patients, the kappa statistic was 0.87 and 1.0 for LGI1 and CASPR2 antibodies respectively.
We demonstrated that a high proportion of patients with very high VGKC-complex antibody levels and relevant clinical syndromes have LGI1 and/or CASPR2 antibodies detected by the commercial assay. Our findings lend support to the use of the assay for rapid and reliable detection of LGI1 and CASPR2 antibodies.
不伴有LGI1/CASPR2抗体的VGKC复合物抗体作为神经自身免疫的独立标志物，其存在仍存在争议。此外，缺乏明确界定神经自身免疫的VGKC复合物抗体临界值，使得检测单特异性抗体变得很重要。我们旨在确定一种用于检测VGKC复合物抗体水平极高的患者中LGI1/CASPR2抗体的商业检测方法（德国吕贝克欧蒙公司）的性能特征，并报告其临床血清学关联。
我们在队列中确定了8例VGKC复合物抗体水平最高（中位数2663.5pM，范围933 - 6730pM）且患有VGKC复合物抗体相关综合征的患者（A组）。另外确定了两组；一组患有疑似神经元表面抗体综合征且VGKC复合物抗体阴性（B组，n = 8），另一组患有小脑共济失调且肿瘤相关神经元抗体阴性（C组，n = 8）。
A组8例患者中有7例（87.5%）存在LGI1和/或CASPR2抗体。B组有1例患者存在LGI1抗体，但在活细胞检测重新检测时为阴性。C组患者均无单特异性抗体。评分者间信度较高；合并A组和B组患者，LGI1和CASPR2抗体的kappa统计量分别为0.87和1.0。
我们证明，VGKC复合物抗体水平极高且有相关临床综合征的患者中，很大一部分通过商业检测可检测到LGI1和/或CASPR2抗体。我们的研究结果支持使用该检测方法快速可靠地检测LGI1和CASPR2抗体。
