Improving the antibody-based evaluation of autoimmune encephalitis.
Improving the antibody-based evaluation of autoimmune encephalitis.
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DOI：
10.1212/nxi.0000000000000404
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发表时间：
2017-11
期刊：
影响因子：
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通讯作者：
Lancaster E
中科院分区：
文献类型：
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作者：
McCracken L;Zhang J;Greene M;Crivaro A;Gonzalez J;Kamoun M;Lancaster E
我们测试了与单独的标准临床测试相比，用额外的研究测定对疑似自身免疫性脑炎患者的抗体筛查样本是否会改善自身免疫性脑炎的检测。我们检查了731个样本（333份CSF、182份血清和108对）来自一组623名患者，这些患者在24个月内由宾夕法尼亚大学临床实验室使用基于细胞的测定（CBA）在市售固定细胞载玻片上检测了针对NMDA受体（NMDAR）的抗体，α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）、γ-氨基丁酸-B受体（GABABR）、富亮氨酸神经胶质瘤失活1（LGI 1）、接触素相关蛋白样2（Caspr 2）和谷氨酸脱羧酶（GAD 65）。同时，我们的研究实验室使用内部CBA筛选了所有样本的脑切片反应性和抗NMDAR。用CBA检查具有脑反应性或阳性临床研究的样品，以获得更大的抗体组。临床实验室报告了NMDAR（80份样本）、GAD 65（8份）、LGI 1（5份）、Caspr 2（2份）和GABABR（4份）的阳性结果。65份血清样本和32份CSF样本的一种或多种抗体不确定。在我们的研究实验室中，除4个阳性结果外，所有阳性结果均得到确认，97个不确定结果中的88个得到解决，另外15个样本被发现为阳性（10个NMDAR，1个AMPAR，3个LGI 1和1个Caspr 2）。临床信息支持这些诊断。总体而言，在15.5%的病例中检测到了信息性自身抗体。标准的临床实验室试剂盒具有特异性，但有些检测不敏感，容易产生不确定的结果。免疫组化筛查脑切片的反应性，然后对脑反应性病例进行额外的CBA，提高了自身免疫性脑炎检测的诊断准确性。
We tested whether antibody screening samples of patients with suspected autoimmune encephalitis with additional research assays would improve the detection of autoimmune encephalitis compared with standard clinical testing alone. We examined 731 samples (333 CSF, 182 sera, and 108 pairs) from a cohort of 623 patients who were tested for CNS autoantibodies by the University of Pennsylvania clinical laboratory over a 24-month period with cell-based assays (CBAs) on commercially obtained slides of fixed cells for antibodies to NMDA receptor (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), γ-aminobutyric acid-B receptor (GABABR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (Caspr2), and glutamic acid decarboxylase (GAD65). In parallel, our research laboratory screened all samples for reactivity to brain sections and for anti-NMDAR using in-house CBAs. Samples with brain reactivity or positive clinical studies were examined with CBAs for a larger panel of antibodies. The clinical laboratory reported positive findings for NMDAR (80 samples), GAD65 (8), LGI1 (5), Caspr2 (2), and GABABR (4). Sixty-five serum samples and 32 CSF samples were indeterminate for one or more antibodies. In our research laboratory, all but 4 positive results were confirmed, 88 of 97 indeterminate results were resolved, and 15 additional samples were found positive (10 NMDAR, 1 AMPAR, 3 LGI1, and 1 Caspr2). Clinical information supported these diagnoses. Overall, informative autoantibodies were detected in 15.5% of cases. Standard clinical laboratory kits were specific, but some tests were insensitive and prone to indeterminate results. Screening with immunohistochemistry for reactivity to brain sections, followed by additional CBAs for cases with brain reactivity, improves the diagnostic accuracy of testing for autoimmune encephalitis.