中国四种遗传性朊病毒病患者脑脊液样本中钙调蛋白的不同反应特征。
Different reactive profiles of calmodulin in the CSF samples of Chinese patients of four types of genetic prion diseases.
作者信息
Jia Xiao-Xi, Hu Chao, Chen Cao, Gao Li-Ping, Liang Dong-Lin, Zhou Wei, Cao Run-Dong, Xiao Kang, Shi Qi, Dong Xiao-Ping
机构信息
National Key-Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Xuanwu Hospital Capital Medical University, Beijing, China.
出版信息
Front Mol Neurosci. 2024 Feb 8;17:1341886. doi: 10.3389/fnmol.2024.1341886. eCollection 2024.
BACKGROUND AND PURPOSE
Calmodulin (CaM) levels exhibit significant elevation in the brain tissue of rodent and cell line models infected with prion, as well as in the cerebrospinal fluid (CSF) samples from patients diagnosed with sporadic Creutzfeldt-Jakob disease (sCJD). However, the status of CSF CaM in patients with genetic prion diseases (gPrDs) remains unclear. This study aims to assess the characteristics of CSF CaM in Chinese patients presenting four subtypes of gPrDs.
METHODS
A total of 103 CSF samples from patients diagnosed with T188K-gCJD, E200K-gCJD, D178N-FFI, P102L-GSS were included in this study, along with 40 CSF samples from patients with non-prion diseases (non-PrDs). The presence of CSF CaM and 14-3-3 proteins was assessed using Western blots analysis, while levels of CSF 14-3-3 and total tau were measured using enzyme-linked immunosorbent assays (ELISAs). Statistical methods including multivariate logistic regression were employed to evaluate the association between CSF CaM positivity and relevant clinical, laboratory, and genetic factors.
RESULTS
The positive rates of CSF CaM were significantly higher in cases of T188K-gCJD (77.1%), E200K-gCJD (86.0%), and P102-GSS (90.9%) compared to non-PrD cases (22.5%). In contrast, CSF CaM positivity was slightly elevated in D178N-FFI (34.3%). CSF CaM positivity was remarkably high in patients who tested positive for CSF 14-3-3 by Western blot and exhibited high levels of total tau (≥1400 pg/ml) as measures by ELISA. Multivariate logistic regression analysis confirmed a significant association between CSF CaM positivity and specific mutations in , as well as with CSF 14-3-3 positivity. Furthermore, the diagnostic performance of CaM surpassed that of 14-3-3 and tau when analyzing CSF samples from T188K-gCJD and E200K-gCJD patients.
CONCLUSION
Western blot analysis reveals significant variations in the positivity of CSF CaM among the four genotypes of gPrD cases, demonstrating a positive correlation with 14-3-3 positivity and elevated tau levels in CSF.
背景与目的
在感染朊病毒的啮齿动物脑组织和细胞系模型中，以及在被诊断为散发性克雅氏病（sCJD）患者的脑脊液（CSF）样本中，钙调蛋白（CaM）水平显著升高。然而，遗传性朊病毒病（gPrDs）患者脑脊液中CaM的状况仍不清楚。本研究旨在评估呈现四种gPrDs亚型的中国患者脑脊液中CaM的特征。
方法
本研究共纳入103例被诊断为T188K - gCJD、E200K - gCJD、D178N - FFI、P102L - GSS患者的脑脊液样本，以及40例非朊病毒病（non - PrDs）患者的脑脊液样本。采用蛋白质免疫印迹分析评估脑脊液中CaM和14 - 3 - 3蛋白的存在情况，同时使用酶联免疫吸附测定（ELISA）测量脑脊液中14 - 3 - 3和总tau的水平。采用包括多变量逻辑回归在内的统计方法评估脑脊液CaM阳性与相关临床、实验室和遗传因素之间的关联。
结果
与非PrD病例（22.5%）相比，T188K - gCJD（77.1%）、E200K - gCJD（86.0%）和P102 - GSS（90.9%）病例中脑脊液CaM的阳性率显著更高。相比之下，D178N - FFI中脑脊液CaM阳性率略有升高（34.3%）。通过蛋白质免疫印迹检测脑脊液14 - 3 - 3呈阳性且通过ELISA检测显示总tau水平高（≥1400 pg/ml）的患者中，脑脊液CaM阳性率非常高。多变量逻辑回归分析证实脑脊液CaM阳性与特定突变以及脑脊液14 - 3 - 3阳性之间存在显著关联。此外，在分析T188K - gCJD和E200K - gCJD患者的脑脊液样本时，CaM的诊断性能超过了14 - 3 - 3和tau。
结论
蛋白质免疫印迹分析显示，gPrD病例的四种基因型中脑脊液CaM的阳性率存在显著差异，表明其与脑脊液中14 - 3 - 3阳性和tau水平升高呈正相关。
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