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κ 轻链在脑脊液中的应用作为多发性硬化症诊断的生物标志物:诊断算法的开发。

Application of κ free light chains in cerebrospinal fluid as a biomarker in multiple sclerosis diagnosis: development of a diagnosis algorithm.

机构信息

Hospital Universitario Virgen de la Victoria, Laboratorio Clinico, Distrito Universitario Teatinos, Campus Teatinos s/n, Málaga 29010, Spain.

Hospital Universitario Virgen de la Victoria, Laboratorio Clinico, Distrito Universitario Teatinos, Málaga, Spain.

出版信息

Clin Chem Lab Med. 2018 Mar 28;56(4):609-613. doi: 10.1515/cclm-2017-0285.

DOI:10.1515/cclm-2017-0285
PMID:29087953
Abstract

BACKGROUND

The determination of κ free light chains (KFLC) in cerebrospinal fluid (CSF) by nephelometry is a feasible alternative to immunoglobulin G oligoclonal bands (OCB) in the evaluation of intrathecal synthesis of immunoglobulin in multiple sclerosis (MS) and other demyelinating diseases. The aim of this study was to assess the diagnostic value of KFLC and its inclusion in a procedure algorithm along with OCB interpretation.

METHODS

A cross-sectional study, which included 123 patients with a CSF OCB request, was carried out. Isoelectric focusing followed by immunofixation was used to detect OCB, and nephelometry was used to analyze KFLC. The KFLC index was calculated using CSF/serum quotient of KFLC and albumin. The KFLC index was compared with MS diagnosis to find the optimal cutoff. It was obtained from the receiver operating characteristic (ROC) curves and the Youden method.

RESULTS

The CSF KFLC median was 1.66 mg/L in the MS group, whereas in other central nervous system diseases, KFLC showed generally no or only moderate increase in CSF (median 0.10 mg/L). KFLC index showed a significant difference between groups. ROC analysis for CSF KFLC concentration, and KFLC indexes were 91.88% and 93.94%, respectively. The best cutoff for the KFLC index was 2.91 for MS diagnosis (sensitivity: 83.78%; specificity: 85.88%). The proposed algorithm showed high sensitivity (89.19%) and specificity (84.71%).

CONCLUSIONS

KFLC determination is rapid and automatized, but it has no higher sensitivity and specificity than OCB in MS diagnosis. Nevertheless, when used in screening, it could reduce the number of manual OCB tests.

摘要

背景

通过散射比浊法测定脑脊液(CSF)中的κ 游离轻链(KFLC),是评估多发性硬化症(MS)和其他脱髓鞘疾病中免疫球蛋白鞘内合成的可行替代方法,替代免疫球蛋白 IgG 寡克隆带(OCB)。本研究旨在评估 KFLC 的诊断价值,并将其与 OCB 解读一起纳入程序算法中。

方法

进行了一项横断面研究,纳入了 123 例 CSF OCB 请求患者。采用等电聚焦-免疫固定电泳法检测 OCB,散射比浊法分析 KFLC。使用 CSF/血清 KFLC 和白蛋白的比值计算 KFLC 指数。通过受试者工作特征(ROC)曲线和 Youden 法,比较 KFLC 指数与 MS 诊断,以确定最佳截断值。

结果

MS 组 CSF KFLC 中位数为 1.66mg/L,而在其他中枢神经系统疾病中,CSF 中 KFLC 通常无或仅有中度增加(中位数 0.10mg/L)。KFLC 指数在各组之间有显著差异。CSF KFLC 浓度和 KFLC 指数的 ROC 分析分别为 91.88%和 93.94%。KFLC 指数的最佳截断值为 2.91,用于 MS 诊断(敏感性:83.78%;特异性:85.88%)。所提出的算法具有较高的敏感性(89.19%)和特异性(84.71%)。

结论

KFLC 测定快速且自动化,但在 MS 诊断中,其敏感性和特异性均不如 OCB。然而,在筛查中,它可以减少手动 OCB 测试的数量。

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