Diagnosis of Human Prion Disease Using Real-Time Quaking-Induced Conversion Testing of Olfactory Mucosa and Cerebrospinal Fluid Samples
Diagnosis of Human Prion Disease Using Real-Time Quaking-Induced Conversion Testing of Olfactory Mucosa and Cerebrospinal Fluid Samples
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DOI：
10.1001/jamaneurol.2016.4614
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发表时间：
2017-02-01
期刊：
影响因子：
29
通讯作者：
Zanusso, Gianluigi
中科院分区：
文献类型：
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作者：
Bongianni, Matilde;Orru, Christina;Zanusso, Gianluigi
重要性克雅氏病（CJD）的早期和准确的体内诊断对于快速区分可治疗和不可治疗的快速进展性痴呆以及未来的治疗试验是必要的。这种早期诊断正在成为可能，使用实时振荡诱导转换（RT-QulC）接种试验，检测微量的疾病特异性病理朊蛋白在脑脊液（CSF）或嗅粘膜（OM）samples. ObjectiveTo发展一种算法，准确和早期诊断克雅氏病，通过使用RT-QulC试验对CSF样品，OM样品，或两者。在这项病例对照研究中，收集了86例临床诊断为可能（n=51）、可能（n=24）或疑似（n=11）CJD患者的CSF和OM样本，以及104例阴性对照样本（54例CSF和50例OM）。使用常规RT-QulC分析CSF和OM样品。使用改进的RT-QuIC条件对CSF样品进行进一步检测。此外，评价了一种新型、易于使用、温和的植绒拭子用于OM采样的诊断性能。资料收集于2015年1月1日至6月30日。主要观察指标：入选患者RT-QuIC检测结果与最终诊断的相关性。（37名男性[43%]和49名女性[57%];平均[SD]年龄，65.7 [11.5]岁）纳入分析，所有61例散发性CJD患者使用OM或CSF样本或两者均具有阳性RT-QuIC结果，总体RT-QuIC诊断灵敏度为100%（95% Cl，93%-100%）。最终诊断为非朊病毒疾病的所有患者（71份CSF和67份OM样本）的RT-QuIC结果均为阴性，特异性为100%（95% CI，94%-100%）。在8例具有引起CJD或Gerstmann-Strussler-Scheinker综合征的各种突变的症状性患者中，6例RT-QuIC结果为阳性，2例为阴性，敏感性为75%。（95%可信区间，结论和相关性散发性CJD的建议诊断算法结合CSF和OM RT-QuIC测试，以提供几乎100%的在疾病的临床阶段的诊断灵敏度和特异性。
IMPORTANCE Early and accurate in vivo diagnosis of Creutzfeldt-Jakob disease (CJD) is necessary for quickly distinguishing treatable from untreatable rapidly progressive dementias and for future therapeutic trials. This early diagnosis is becoming possible using the real-time quaking-induced conversion (RT-QulC) seeding assay, which detects minute amounts of the disease-specific pathologic prion protein in cerebrospinal fluid (CSF) or olfactory mucosa ( OM) samples.OBJECTIVE To develop an algorithm for accurate and early diagnosis of CJD by using the RT-QulC assay on CSF samples, OM samples, or both.DESIGN, SETTING, AND PARTICIPANTS In this case-control study, samples of CSF and OM were collected from 86 patients with a clinical diagnosis of probable (n=51), possible (n=24), or suspected (n=11) CJD and 104 negative control samples (54 CSF and 50 OM). The CSF and OM samples were analyzed using conventional RT-QulC. The CSF samples underwent further testing using improved RT-QuIC conditions. In addition, the diagnostic performance of a novel, easy-to-use, gentle flocked swab for sampling of OM was evaluated. Data were collected from January 1 to June 30, 2015.MAIN OUTCOME AND MEASURES Correlations between RT-QuIC results and the final diagnosis of recruited patients.RESULTS Among the 86 patients (37 men [43%] and 49 women [57%];mean [SD] age, 65.7 [11.5] years) included for analysis, all 61 patients with sporadic CJD had positive RT-QuIC findings using OM or CSF samples or both for an overall RT-QuIC diagnostic sensitivity of 100% (95% Cl, 93%-100%). All patients with a final diagnosis of non-prion disease (71 CSF and 67 OM samples) had negative RT-QuIC findings for 100% specificity ( 95% CI, 94%-100%). Of 8 symptomatic patients with various mutations causing CJD or Gerstmann-Strussler-Scheinker syndrome, 6 had positive and 2 had negative RT-QuIC findings for a sensitivity of 75%( 95% CI, 36%-96%).CONCLUSIONS AND RELEVANCE A proposed diagnostic algorithm for sporadic CJD combines CSF and OM RT-QuIC testing to provide virtually 100% diagnostic sensitivity and specificity in the clinical phase of the disease.