Decreased CSF transferrin in sCJD: a potential pre-mortem diagnostic test for prion disorders.
Decreased CSF transferrin in sCJD: a potential pre-mortem diagnostic test for prion disorders.
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DOI：
10.1371/journal.pone.0016804
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发表时间：
2011-03-09
期刊：
影响因子：
3.7
通讯作者：
Singh N
中科院分区：
文献类型：
--
作者：
Singh A;Beveridge AJ;Singh N
散发性克雅氏病（sCJD）是一种致命的神经退行性疾病，直到尸检才能发现。最近有报道称，在sCJD病例中，脑铁平衡失调伴随着转铁蛋白（Tf）的增加。这种异常对脑脊液（CSF） Tf水平的影响尚不确定。我们评估了CSF Tf（一种“新的”生物标志物）单独使用或与“当前的”生物标志物total-tau （T-tau）联合使用作为sCJD的死前诊断测试的准确性。在死亡前0.3-36个月（持续时间）收集99例尸检确诊的sCJD （CJD+）和75例确诊的非CJD源性痴呆（CJD-）患者的脑脊液中，对总Tf （T-Tf）、Tf亚型（Tf-1和Tf-β2）和Tf铁饱和度进行了定量分析。通过非参数检验、逻辑回归和受试者工作特征（ROC）分析来评估诊断准确性。计算各生物标志物及生物标志物组合的ROC曲线下面积（AUC）、敏感性、特异性、阳性预测值和阴性预测值（PV）以及似然比（LR）。我们报道，相对于CJD-， CJD+病例有较低的中位CSF T-Tf（125,7093比217,7893）和较高的T-tau（11530比1266）值。T-Tf的AUC为0.90(95%可信区间（CI）， 0.85-0.94)， T-Tf联合T-tau的AUC为0.93 （95% CI, 0.89-0.97）。T-Tf识别CJD+病例的特异性为71.6% (95% CI, 59.1-81.7)，阳性LR为3.0 (95% CI, 2.1-4.5)，阴性LR为0.2 (95% CI, 0.1-0.3)，准确率为80.1%。患者年龄和病程的影响不显著。T-Tf联合T-tau鉴定CJD+的特异性为87.5% (95%CI, 76.3-94.1)，阳性LR为6.8 (95%CI, 3.5-13.1)，阴性LR为0.2 (95%CI, 0.1-0.3)，阳性pv为91.0%，阴性pv为80.0%，准确率为86.2%。因此，CSF T-Tf，一种新的生物标志物，当与当前的生物标志物T-tau结合使用时，是一种可靠的sCJD死前诊断测试。
Sporadic Creutzfeldt-Jakob-disease (sCJD) is a fatal neurodegenerative condition that escapes detection until autopsy. Recently, brain iron dyshomeostasis accompanied by increased transferrin (Tf) was reported in sCJD cases. The consequence of this abnormality on cerebrospinal-fluid (CSF) levels of Tf is uncertain. We evaluated the accuracy of CSF Tf, a ‘new’ biomarker, as a pre-mortem diagnostic test for sCJD when used alone or in combination with the ‘current’ biomarker total-tau (T-tau). Levels of total-Tf (T-Tf), isoforms of Tf (Tf-1 and Tf-β2), and iron saturation of Tf were quantified in CSF collected 0.3–36 months before death (duration) from 99 autopsy confirmed sCJD (CJD+) and 75 confirmed cases of dementia of non-CJD origin (CJD-). Diagnostic accuracy was estimated by non-parametric tests, logistic regression, and receiver operating characteristic (ROC) analysis. Area under the ROC curve (AUC), sensitivity, specificity, positive and negative predictive values (PV), and likelihood ratios (LR) of each biomarker and biomarker combination were calculated. We report that relative to CJD-, CJD+ cases had lower median CSF T-Tf (125,7093 vs. 217,7893) and higher T-tau (11530 vs. 1266) values. AUC was 0.90 (95% confidence interval (CI), 0.85–0.94) for T-Tf, and 0.93 (95% CI, 0.89–0.97) for T-Tf combined with T-tau. With cut-offs defined to achieve a sensitivity of ∼85%, T-Tf identified CJD+ cases with a specificity of 71.6% (95% CI, 59.1–81.7), positive LR of 3.0 (95% CI, 2.1–4.5), negative LR of 0.2 (95% CI, 0.1–0.3), and accuracy of 80.1%. The effect of patient age and duration was insignificant. T-Tf combined with T-tau identified CJD+ with improved specificity of 87.5% (95%CI, 76.3–94.1), positive LR of 6.8 (95% CI, 3.5–13.1), negative LR of 0.2 (95% CI, 0.1–0.3), positive-PV of 91.0%, negative-PV of 80.0%, and accuracy of 86.2%. Thus, CSF T-Tf, a new biomarker, when combined with the current biomarker T-tau, is a reliable pre-mortem diagnostic test for sCJD.
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