Zeman David, Kušnierová Pavlína, Švagera Zdeněk, Všianský František, Byrtusová Monika, Hradílek Pavel, Kurková Barbora, Zapletalová Olga, Bartoš Vladimír
Institute of Laboratory Diagnostics, University Hospital Ostrava, 17. listopadu 1790, 708 52 Ostrava-Poruba, Czech Republic.
Clinic of Neurology, University Hospital Ostrava, 17. listopadu 1790, 708 52 Ostrava-Poruba, Czech Republic.
PLoS One. 2016 Nov 15;11(11):e0166556. doi: 10.1371/journal.pone.0166556. eCollection 2016.
We aimed to compare various methods for free light chain (fLC) quantitation in cerebrospinal fluid (CSF) and serum and to determine whether quantitative CSF measurements could reliably predict intrathecal fLC synthesis. In addition, we wished to determine the relationship between free kappa and free lambda light chain concentrations in CSF and serum in various disease groups.
We analysed 166 paired CSF and serum samples by at least one of the following methods: turbidimetry (Freelite™, SPAPLUS), nephelometry (N Latex FLC™, BN ProSpec), and two different (commercially available and in-house developed) sandwich ELISAs. The results were compared with oligoclonal fLC detected by affinity-mediated immunoblotting after isoelectric focusing.
Although the correlations between quantitative methods were good, both proportional and systematic differences were discerned. However, no major differences were observed in the prediction of positive oligoclonal fLC test. Surprisingly, CSF free kappa/free lambda light chain ratios were lower than those in serum in about 75% of samples with negative oligoclonal fLC test. In about a half of patients with multiple sclerosis and clinically isolated syndrome, profoundly increased free kappa/free lambda light chain ratios were found in the CSF.
Our results show that using appropriate method-specific cut-offs, different methods of CSF fLC quantitation can be used for the prediction of intrathecal fLC synthesis. The reason for unexpectedly low free kappa/free lambda light chain ratios in normal CSFs remains to be elucidated. Whereas CSF free kappa light chain concentration is increased in most patients with multiple sclerosis and clinically isolated syndrome, CSF free lambda light chain values show large interindividual variability in these patients and should be investigated further for possible immunopathological and prognostic significance.
我们旨在比较脑脊液（CSF）和血清中游离轻链（fLC）定量的各种方法，并确定脑脊液定量测量是否能可靠地预测鞘内fLC合成。此外，我们希望确定不同疾病组脑脊液和血清中游离κ和游离λ轻链浓度之间的关系。
我们通过以下至少一种方法分析了166对脑脊液和血清样本：比浊法（Freelite™，SPAPLUS）、散射比浊法（N Latex FLC™，BN ProSpec）以及两种不同的（市售和自行研发的）夹心酶联免疫吸附测定法。将结果与等电聚焦后通过亲和介导免疫印迹检测的寡克隆fLC进行比较。
尽管定量方法之间的相关性良好，但比例差异和系统差异均有体现。然而，在预测寡克隆fLC检测阳性方面未观察到重大差异。令人惊讶的是，在约75%寡克隆fLC检测阴性的样本中，脑脊液游离κ/游离λ轻链比值低于血清中的比值。在约一半的多发性硬化症和临床孤立综合征患者中，脑脊液中游离κ/游离λ轻链比值显著升高。
我们的结果表明，使用适当的方法特异性临界值，不同的脑脊液fLC定量方法可用于预测鞘内fLC合成。正常脑脊液中游离κ/游离λ轻链比值意外偏低的原因仍有待阐明。虽然大多数多发性硬化症和临床孤立综合征患者的脑脊液游离κ轻链浓度升高，但这些患者的脑脊液游离λ轻链值个体间差异较大，应进一步研究其可能具有的免疫病理学和预后意义。
