Süße Marie, Reiber Hansotto, Grothe Matthias, Petersmann Astrid, Nauck Matthias, Dressel Alexander, Hannich Malte Johannes
Departement of Neurology, University Medicine Greifswald, Greifswald, Germany.
CSF and Complexity Studies, Göttingen and University Göttingen, Germany.
J Neuroimmunol. 2020 Jun 12;346:577287. doi: 10.1016/j.jneuroim.2020.577287.
Free light chain kappa (FLC-k) in cerebrospinal fluid (CSF) is involved in intrathecal immune responses and is being investigated frequently for its diagnostic sensitivity. The objective of this study was the application and interpretation of FLC-k data in quotient diagrams with a hyperbolic reference range and to confirm the superior evaluation in comparison with another proposed reference method and cut-off values. Secondly, the performance of the FLC-k quotient diagram was analyzed in respect to MS and CIS patients and in relation to the polyspecific immune response.
FLC-k was analyzed in a control cohort (n = 302) and in patients with MS/CIS (n = 98) using a nephelometric FLC-k kit. The intrathecal fraction of FLC-k based on the hyperbolic reference range was calculated in comparison to various linear FLC-k indices and routine CSF parameters [oligoclonal bands (OCB), polyspecific antiviral immune response].
Using the new hyperbolic reference range, intrathecal FLC-k synthesis was found in 20 / 302 OCB negative controls. The sensitivity in the definitive MS cohort was 100%, compared to 93% positive OCB. The linear FLC-k Index interpretation with similar sensitivity for MS, however, bares the risk for the control samples,depending on the reference range, of false positive interpretations (up to 7 at low QAlb) or false negative interpretations (up to 17/20 FLC-k positives at high QAlb). The quantitative mean intrathecal FLC-k synthesis in the CIS cohort (later MS) was even slightly higher than in initially definitive MS questioning a pathophysiological difference. A positive MRZ reaction found in 53% percent of CIS patients with intrathecal FLC-k synthesis could have allowed diagnosis of MS immediately, i.e. earlier than with the Mc Donald criteria.
The evaluation of FLC-k with hyperbolic reference range in quotient diagrams is superior to other analytical methods like the linear FLC-k index. We suggest a sequential CSF testing with FLC-k Reibergram evaluation, potentially followed by isoelectric focusing. With the MRZ reaction we obtain highest specificity for MS diagnosis.
脑脊液（CSF）中的游离轻链κ（FLC-κ）参与鞘内免疫反应，其诊断敏感性正受到频繁研究。本研究的目的是在具有双曲线参考范围的商图中应用和解释FLC-κ数据，并与另一种提议的参考方法和临界值进行比较，以确认其更高的评估价值。其次，针对多发性硬化症（MS）和临床孤立综合征（CIS）患者，以及与多特异性免疫反应相关的情况，分析了FLC-κ商图的性能。
使用散射比浊法FLC-κ检测试剂盒，对一个对照组（n = 302）以及MS/CIS患者（n = 98）进行FLC-κ分析。与各种线性FLC-κ指标和常规CSF参数[寡克隆带（OCB）、多特异性抗病毒免疫反应]相比，计算基于双曲线参考范围的FLC-κ鞘内分数。
使用新的双曲线参考范围，在20/302例OCB阴性对照中发现了鞘内FLC-κ合成。在确诊的MS队列中，敏感性为100%，而OCB阳性率为93%。对于MS，线性FLC-κ指数解释具有相似的敏感性，但对于对照样本，根据参考范围，存在假阳性解释（低QAlb时高达7例）或假阴性解释（高QAlb时高达17/20例FLC-κ阳性）的风险。CIS队列（后来发展为MS）中鞘内FLC-κ合成的定量平均值甚至略高于最初确诊的MS患者，这对病理生理差异提出了质疑。在53%具有鞘内FLC-κ合成的CIS患者中发现的阳性MRZ反应本可以立即诊断出MS，即比使用麦克唐纳标准更早。
在商图中使用双曲线参考范围评估FLC-κ优于其他分析方法，如线性FLC-κ指数。我们建议进行FLC-κ赖伯格图评估的序贯CSF检测，可能随后进行等电聚焦。通过MRZ反应，我们获得了MS诊断的最高特异性。
