PDF(Pubmed)
Abstract：
UNASSIGNED: Cerebrospinal fluid (CSF) kappa free light chain (κFLC) measures gained increasing interest as diagnostic markers in multiple sclerosis (MS). However, the lack of studies comparing assay-dependent diagnostic cutoff values hinders their use in clinical practice. Additionally, the optimal κFLC parameter for identifying MS remains a subject of ongoing debate.
UNASSIGNED: The aim of this study was to compare same-sample diagnostic accuracies of the κFLC index, κIgG index, CSF κFLC/IgG ratio, and isolated CSF κFLC (iCSF-κFLC) between two reference centers using different methods.
UNASSIGNED: Paired serum and CSF samples were analyzed for κFLC and albumin concentrations by Freelite®-Optilite (Sint-Jan Bruges hospital) and N Latex®-BNII (Ghent University hospital). Diagnostic performance to differentiate MS from controls was assessed using ROC curve analysis.
UNASSIGNED: A total of 263 participants were included (MS, n = 80). Optimal diagnostic cutoff values for the κFLC index (Freelite®-Optilite: 7.7; N Latex®-BNII: 4.71), κIgG index (Freelite®-Optilite: 14.15, N Latex®-BNII: 12.19), and CSF κFLC/IgG ratio (Freelite®-Optilite: 2.27; N Latex®-BNII: 1.44) differed between the two methods. Sensitivities related to optimal cutoff values were 89.9% (Freelite®-Optilite) versus 94.6% (N Latex®-BNII) for the κFLC index, 91% (Freelite®-Optilite) versus 92.2% (N Latex®-BNII) for the κIgG index, and 81.3% (Freelite®-Optilite) versus 91.4% (N Latex®-BNII) for the CSF κFLC/IgG ratio. However, for iCSF-κFLC, optimal diagnostic cutoff values (0.36 mg/L) and related specificities (81.8%) were identical with a related diagnostic sensitivity of 89.9% for Freelite®-Optilite and 90.5% for N Latex®-BNII. The diagnostic performance of the κFLC index [area under the curve (AUC) Freelite®-Optilite: 0.924; N Latex®-BNII: 0.962] and κIgG index (AUC Freelite®-Optilite: 0.929; N Latex®-BNII: 0.961) was superior compared to CSF oligoclonal bands (AUC: 0.898, sensitivity: 83.8%, specificity: 95.9%).
UNASSIGNED: The κFLC index and the κIgG index seem to be excellent markers for identifying MS, irrespective of the method used for κFLC quantification. Based on the AUC, they appear to be the measures of choice. For all measures, optimal cutoff values differed between methods except for iCSF-κFLC. iCSF-κFLC might therefore serve as a method-independent, more cost-efficient, initial screening measure for MS. These findings are particularly relevant for clinical practice given the potential future implementation of intrathecal κFLC synthesis in MS diagnostic criteria and for future multicentre studies pooling data on κFLC measures.
UNASSIGNED: The aim of this study was to compare same-sample diagnostic accuracies of the κFLC index, κIgG index, CSF κFLC/IgG ratio, and isolated CSF κFLC (iCSF-κFLC) between two reference centers using different methods.
UNASSIGNED: Paired serum and CSF samples were analyzed for κFLC and albumin concentrations by Freelite®-Optilite (Sint-Jan Bruges hospital) and N Latex®-BNII (Ghent University hospital). Diagnostic performance to differentiate MS from controls was assessed using ROC curve analysis.
UNASSIGNED: A total of 263 participants were included (MS, n = 80). Optimal diagnostic cutoff values for the κFLC index (Freelite®-Optilite: 7.7; N Latex®-BNII: 4.71), κIgG index (Freelite®-Optilite: 14.15, N Latex®-BNII: 12.19), and CSF κFLC/IgG ratio (Freelite®-Optilite: 2.27; N Latex®-BNII: 1.44) differed between the two methods. Sensitivities related to optimal cutoff values were 89.9% (Freelite®-Optilite) versus 94.6% (N Latex®-BNII) for the κFLC index, 91% (Freelite®-Optilite) versus 92.2% (N Latex®-BNII) for the κIgG index, and 81.3% (Freelite®-Optilite) versus 91.4% (N Latex®-BNII) for the CSF κFLC/IgG ratio. However, for iCSF-κFLC, optimal diagnostic cutoff values (0.36 mg/L) and related specificities (81.8%) were identical with a related diagnostic sensitivity of 89.9% for Freelite®-Optilite and 90.5% for N Latex®-BNII. The diagnostic performance of the κFLC index [area under the curve (AUC) Freelite®-Optilite: 0.924; N Latex®-BNII: 0.962] and κIgG index (AUC Freelite®-Optilite: 0.929; N Latex®-BNII: 0.961) was superior compared to CSF oligoclonal bands (AUC: 0.898, sensitivity: 83.8%, specificity: 95.9%).
UNASSIGNED: The κFLC index and the κIgG index seem to be excellent markers for identifying MS, irrespective of the method used for κFLC quantification. Based on the AUC, they appear to be the measures of choice. For all measures, optimal cutoff values differed between methods except for iCSF-κFLC. iCSF-κFLC might therefore serve as a method-independent, more cost-efficient, initial screening measure for MS. These findings are particularly relevant for clinical practice given the potential future implementation of intrathecal κFLC synthesis in MS diagnostic criteria and for future multicentre studies pooling data on κFLC measures.
摘要：
■脑脊液（CSF）κ游离轻链（κFLC）测量作为多发性硬化症（MS）的诊断标记物获得了越来越多的兴趣。然而,缺乏比较测定依赖性诊断临界值的研究,阻碍了它们在临床实践中的应用.此外,用于识别MS的最佳κFLC参数仍然是一个正在进行辩论的主题。
■这项研究的目的是比较κFLC指数的相同样本诊断准确性，κIgG指数,CSFκFLC/IgG比值,和使用不同方法在两个参考中心之间分离的CSFκFLC（iCSF-κFLC）。
通过Freelite®-Optilite(Sint-JanBruges医院)和NLatex®-BNII(根特大学医院)分析配对血清和CSF样品的κFLC和白蛋白浓度。使用ROC曲线分析评估区分MS与对照的诊断性能。
■总共包括263名参与者(MS，n=80)。κFLC指数的最佳诊断临界值（Freelite®-Optilite：7.7；NLatex®-BNII：4.71），κIgG指数（Freelite®-Optilite：14.15，NLatex®-BNII：12.19），和CSFκFLC/IgG比率(Freelite®-Optilite:2.27;NLatex®-BNII:1.44)在两种方法之间不同。κFLC指数与最佳截止值相关的灵敏度为89.9%(Freelite®-Optilite)与94.6%(NLatex®-BNII),κIgG指数为91％（Freelite®-Optilite）与92.2％（NLatex®-BNII），CSFκFLC/IgG比率为81.3%(Freelite®-Optilite)对91.4%(NLatex®-BNII)。然而,对于iCSF-κFLC，最佳诊断临界值(0.36mg/L)和相关特异性(81.8%)相同,Freelite®-Optilite和NLatex®-BNII的相关诊断灵敏度分别为89.9%和90.5%.κFLC指数[曲线下面积（AUC）Freelite®-Optilite：0.924；NLatex®-BNII：0.962]和κIgG指数（AUCFreelite®-Optilite：0.929；NLatex®-BNII：0.961）优于寡克隆CSF条带（AUC：0.898，灵敏度：83.8％，特异性：95.9%）。
■κFLC指数和κIgG指数似乎是鉴定MS的极好标记，与用于κFLC定量的方法无关。基于AUC，它们似乎是选择的措施。对于所有措施，除iCSF-κFLC外，其他方法之间的最佳临界值不同。因此，iCSF-κFLC可能是一种独立于方法的，更具成本效益，MS的初步筛查措施鉴于未来在MS诊断标准中可能实施鞘内κFLC合成，以及未来多中心研究汇集κFLC测量数据，这些发现与临床实践特别相关。
■这项研究的目的是比较κFLC指数的相同样本诊断准确性，κIgG指数,CSFκFLC/IgG比值,和使用不同方法在两个参考中心之间分离的CSFκFLC（iCSF-κFLC）。
通过Freelite®-Optilite(Sint-JanBruges医院)和NLatex®-BNII(根特大学医院)分析配对血清和CSF样品的κFLC和白蛋白浓度。使用ROC曲线分析评估区分MS与对照的诊断性能。
■总共包括263名参与者(MS，n=80)。κFLC指数的最佳诊断临界值（Freelite®-Optilite：7.7；NLatex®-BNII：4.71），κIgG指数（Freelite®-Optilite：14.15，NLatex®-BNII：12.19），和CSFκFLC/IgG比率(Freelite®-Optilite:2.27;NLatex®-BNII:1.44)在两种方法之间不同。κFLC指数与最佳截止值相关的灵敏度为89.9%(Freelite®-Optilite)与94.6%(NLatex®-BNII),κIgG指数为91％（Freelite®-Optilite）与92.2％（NLatex®-BNII），CSFκFLC/IgG比率为81.3%(Freelite®-Optilite)对91.4%(NLatex®-BNII)。然而,对于iCSF-κFLC，最佳诊断临界值(0.36mg/L)和相关特异性(81.8%)相同,Freelite®-Optilite和NLatex®-BNII的相关诊断灵敏度分别为89.9%和90.5%.κFLC指数[曲线下面积（AUC）Freelite®-Optilite：0.924；NLatex®-BNII：0.962]和κIgG指数（AUCFreelite®-Optilite：0.929；NLatex®-BNII：0.961）优于寡克隆CSF条带（AUC：0.898，灵敏度：83.8％，特异性：95.9%）。
■κFLC指数和κIgG指数似乎是鉴定MS的极好标记，与用于κFLC定量的方法无关。基于AUC，它们似乎是选择的措施。对于所有措施，除iCSF-κFLC外，其他方法之间的最佳临界值不同。因此，iCSF-κFLC可能是一种独立于方法的，更具成本效益，MS的初步筛查措施鉴于未来在MS诊断标准中可能实施鞘内κFLC合成，以及未来多中心研究汇集κFLC测量数据，这些发现与临床实践特别相关。
