Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus N, Denmark.
Department of Biomedicine, Aarhus University, Aarhus C, Denmark.
Clin Chem Lab Med. 2018 Dec 19;57(2):210-220. doi: 10.1515/cclm-2018-0400.
Background Detection of intrathecal immunoglobulin G (IgG) synthesis by gold standard oligoclonal bands (OCB) or IgG index remains an integral part of multiple sclerosis (MS) diagnostics, although both methods have weaknesses. Emerging evidence suggests that automated detection of free light chains (FLC) in the cerebrospinal fluid (CSF) has diagnostic performance equal to OCB. The objective of this study was to compare the diagnostic performance of CSF FLC with OCB and IgG index in a large cohort of Scandinavian patients referred for MS evaluation. Methods We prospectively included 230 patients suspected for MS. They are composed of patients with MS (n=96), clinically isolated syndrome (n=37), other neurological diseases (OND, n=31) and symptomatic controls (SC, n=66). CSF and serum samples were analyzed for kappa and lambda FLC, OCB and IgG index. Diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis. Results Both the absolute concentration of CSF-kappa and the kappa index had excellent MS diagnostic performances with ROC area under the curve of 0.93 and 0.94 (MS vs. SC+OND). At the 0.42 mg/L cutoff, CSF-kappa had sensitivity and specificity of 93.8% and 85.6%, whereas sensitivity and specificity for OCB was 82.3% and 93.8% (72.9% and 95.9% for IgG index at cutoff 0.64). CSF-lambda and lambda index performed inferior to CSF-kappa and kappa index. Conclusions CSF-kappa and kappa index represent automated, rapid and low-cost alternatives to OCB. Using merely the absolute concentration of CSF-kappa is a logistic advantage in the clinical laboratories.
背景 金标准寡克隆带(OCB)或 IgG 指数检测鞘内 IgG 合成仍然是多发性硬化症(MS)诊断的一个组成部分,尽管这两种方法都有其弱点。新出现的证据表明,脑脊液(CSF)中游离轻链(FLC)的自动检测具有与 OCB 相等的诊断性能。本研究的目的是在一个大型的斯堪的纳维亚 MS 评估患者队列中,比较 CSF FLC 与 OCB 和 IgG 指数的诊断性能。
方法 我们前瞻性纳入了 230 名疑似 MS 的患者。他们由 MS 患者(n=96)、临床孤立综合征(n=37)、其他神经系统疾病(OND,n=31)和症状性对照(SC,n=66)组成。对 CSF 和血清样本进行了 kappa 和 lambda FLC、OCB 和 IgG 指数的分析。通过接受者操作特征(ROC)分析评估诊断性能。
结果 CSF-kappa 的绝对浓度和 kappa 指数均具有出色的 MS 诊断性能,ROC 曲线下面积分别为 0.93 和 0.94(MS 与 SC+OND)。在 0.42mg/L 截点时,CSF-kappa 的敏感性和特异性分别为 93.8%和 85.6%,而 OCB 的敏感性和特异性分别为 82.3%和 93.8%(OCB 为 72.9%和 95.9%)。CSF-lambda 和 lambda 指数的性能均低于 CSF-kappa 和 kappa 指数。
结论 CSF-kappa 和 kappa 指数是 OCB 的自动化、快速和低成本替代方法。在临床实验室中,仅使用 CSF-kappa 的绝对浓度具有逻辑优势。