The 14-3-3 brain protein in cerebrospinal fluid as a marker for transmissible spongiform encephalopathies
The 14-3-3 brain protein in cerebrospinal fluid as a marker for transmissible spongiform encephalopathies
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DOI：
10.1056/nejm199609263351303
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发表时间：
1996-09-26
影响因子：
158.5
通讯作者：
Harrington, MG
中科院分区：
文献类型：
--
作者：
Hsich, G;Kinney, K;Harrington, MG
研究背景目前尚无实用可靠的克雅氏病及相关传染性海绵状脑病的尸检方法。两种蛋白质，命名为130和131，已在克雅氏病患者的脑脊液中检测到低浓度，似乎是该疾病的敏感和特异性标志物。然而，鉴定这些蛋白质的尝试并不成功。方法我们检测了正常人脑中的蛋白质130和131，并对其氨基酸进行了部分测序，发现它们与脑蛋白14-3-3相匹配。结果71例Creutzfeldt-Jakob病患者中有68例脑脊液中检测到14 - 3 - 3蛋白，其中186例人脑脊液中检测到14-3-3蛋白，30例海绵状脑病患者脑脊液中检测到14-3-3蛋白，94例动物脑脊液中检测到14-3-3蛋白（96%; 95%置信区间，92%至99%）。在94例其他痴呆患者中，特异性为96%。如果排除三名在测试前一个月内中风的痴呆症患者，特异性为99%。在24例病毒性脑炎患者中，12例试验阳性。在动物中的检测的灵敏度为87%，特异性为99%.Conclusions在痴呆患者中，脑脊液中的14-3-3脑蛋白的阳性免疫测定强烈支持Creutzfeldt-Jakob病的诊断。然而，这一发现并不支持在没有临床明显痴呆的患者中使用该测试。
Background There is no practical and reliable premortem test for Creutzfeldt-Jakob disease and the related transmissible spongiform encephalopathies. Two proteins, designated 130 and 131, which have been detected in low concentrations in cerebrospinal fluid from patients with Creutzfeldt-Jakob disease, appear to be sensitive and specific markers for the disease. Attempts to identify these proteins, however, have been unsuccessful. We hypothesized that they may be present in the normal brain.Methods We detected proteins 130 and 131 in normal human brain, partially sequenced their amino acids, and found that they matched the brain protein known as 14-3-3. We then developed a simple, rapid immunoassay for this protein and tested it in cerebrospinal fluid samples from 71 humans and 30 animals with spongiform encephalopathies and in control samples from 186 humans and 94 animals.Results The immunoassay detected the 14-3-3 protein in cerebrospinal fluid from 68 of the 71 patients with Creutzfeldt-Jakob disease (96 percent; 95 percent confidence interval, 92 to 99 percent). Among 94 patients with other dementias, the specificity was 96 percent. If one excludes the three patients with dementia who had had strokes within one month before testing, the specificity was 99 percent. The test was positive in 12 of 24 patients with viral encephalitis. In animals the sensitivity of the assay was 87 percent and the specificity was 99 percent.Conclusions In patients with dementia, a positive immunoassay for the 14-3-3 brain protein in cerebrospinal fluid strongly supports a diagnosis of Creutzfeldt-Jakob disease. This finding, however, does not support the use of the test in patients without clinically evident dementia.