Data from: Diagnostic and prognostic value of the cerebrospinal fluid concentration of immunoglobulin free light chains in clinically isolated syndrome with conversion to multiple sclerosis

Background and objective: In this study, we evaluated the diagnostic and prognostic significance of cerebrospinal fluid free light chains (CSF FLC) at the time of clinically isolated syndrome (CIS). Methods: We compared FLC-parameters at the moment of CIS in patients with conversion to multiple sclerosis (MS) after 2 years (CIS-MS), patients who remained stable both clinically and radiologically after 2 years (CIS-nonMS), patients with non-inflammatory neurologic diseases (NIND) as a comparison group and patients with other inflammatory neurologic diseases (IND) with intrathecal oligoclonal bands (OCB) synthesis. ROC-analysis was conducted to define FLC-assay characteristics and cut-off values. We also compared FLC-concentrations in CIS patients to determine their OCB-status. A correlation analysis was performed between FLC-concentrations and the expanded disability scale score (EDSS), annualized relapse rate (ARR) and MRI-activity (i.e., number of new and gadolinium-enhancing (Gd+) lesions) in patients. Results: The levels of kappa-FLC (k-FLCCSF) and lambda-FLC (λ-FLCCSF) as well as kappa- and lambda-quotients (Q-k and Q-λ) were elevated in CIS-MS compared to the CIS-nonMS and NIND groups. These levels did not differ significantly when compared with the IND group. We identified several patients with high k-FLCCSF and λ-FLCCSF in OCB-negative CIS and IND groups. The level of k-FLCCSF production was significantly higher in OCB-positive patients in the CIS-MS group compared to the CIS-nonMS group. The concentrations of k-FLCCSF and Q-k in the CIS-MS group showed significant correlation with the level of EDSS after 2 years (k-FLC: r = 0.4477,p = 0.0016; Q-k: r = 0.4621, p = 0.0016). λ-FLCCSF and Q-λ inversely correlated with the number of Gd+ lesions (CSF λ-FLC: r = -0.3698, p = 0.0223; Q-λ: r = -0.4527, p = 0.0056). Conclusion: The concentration of CSF FLC predicts conversion to MS within 2 years following CIS. OCB-positive patients with an early conversion have a higher concentration of CSF-FLC. We have also shown a prognostic significance of k-FLCCSF for future EDSS-progression.

研究背景与研究目的：本研究旨在评估临床孤立综合征（clinically isolated syndrome, CIS）发病时脑脊液游离轻链（cerebrospinal fluid free light chains, CSF FLC）的诊断与预后价值。
方法：本研究纳入四类研究对象：2年内转化为多发性硬化（multiple sclerosis, MS）的临床孤立综合征患者（CIS-MS组）、2年内临床与影像学均保持稳定的临床孤立综合征患者（CIS-nonMS组）、非炎症性神经系统疾病（non-inflammatory neurologic diseases, NIND）患者（对照组）以及伴鞘内寡克隆带（intrathecal oligoclonal bands, OCB）合成的其他炎症性神经系统疾病（inflammatory neurologic diseases, IND）患者。本研究比较了各组对象在临床孤立综合征发病时的游离轻链相关参数；采用受试者工作特征（ROC）分析明确游离轻链检测的性能特征与截断值；同时比较不同寡克隆带状态的临床孤立综合征患者的游离轻链浓度；并分析患者的游离轻链浓度与扩展残疾状态量表（expanded disability scale score, EDSS）评分、年复发率（annualized relapse rate, ARR）以及磁共振成像（MRI）活动度（即新增病灶与钆增强（gadolinium-enhancing, Gd+）病灶数量）之间的相关性。
结果：与CIS-nonMS组及NIND组相比，CIS-MS组的κ游离轻链（κ-FLCCSF）、λ游离轻链（λ-FLCCSF）水平以及κ、λ比值（Q-k与Q-λ）均显著升高；而与IND组相比，上述指标无显著差异。在OCB阴性的CIS及IND组中，本研究观察到部分患者的κ-FLCCSF与λ-FLCCSF水平升高。CIS-MS组中OCB阳性患者的κ-FLCCSF生成水平显著高于CIS-nonMS组。CIS-MS组的κ-FLCCSF浓度与Q-k值均与2年后的EDSS评分呈显著正相关（κ-FLC：r=0.4477，p=0.0016；Q-k：r=0.4621，p=0.0016）；λ-FLCCSF与Q-λ值则与Gd+病灶数量呈显著负相关（CSF λ-FLC：r=-0.3698，p=0.0223；Q-λ：r=-0.4527，p=0.0056）。
结论：脑脊液游离轻链浓度可预测临床孤立综合征发病后2年内的多发性硬化转化风险。早期发生转化的OCB阳性患者脑脊液游离轻链浓度更高。本研究同时证实κ-FLCCSF对未来EDSS进展具有预后价值。