Institute of Pediatric Neurology, Schneider Children's Medical Center, Petach Tikva 49202, Israel.
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Clin Chem Lab Med. 2018 Jun 27;56(7):1081-1089. doi: 10.1515/cclm-2017-0911.
Identifying new biomarkers is needed to overcome the diagnostic difficulties of pediatric multiple sclerosis (MS). Recently, we developed a new technique including CSF analysis of free light chain (FLC) monomers and dimers, which can improve diagnosis of adult MS. The present study has been designed to evaluate the utility of our technique for MS diagnosis in children.
Patients with MS (n=21) and non-MS demyelinating or inflammatory neurological disorders (n=35) participated in the study. MS diagnosis was based on clinical and magnetic resonance imaging (MRI) findings. Western blot analysis was applied to examine FLC in the patients' CSF and serum. FLC indices for FLC monomer and dimer levels and κ/λ ratios were estimated. The samples were also analyzed by oligoclonality test.
The study revealed abnormally elevated levels of κ-FLC monomers and dimers in the CSF of 10 MS patients ("κ-type MS"). Increased amounts of λ dimers were found in six MS cases ("λ-type MS"), while high levels of both κ and λ FLC ("mixed type MS") were documented in three MS cases. MRI and clinical assessment showed a more aggressive disease form for the "mixed" and "λ-type" cases. Our method demonstrated higher sensitivity (90.5%) and specificity (91.4%) for discrimination between MS and non-MS patients, as compared to oligoclonality test (81% and 65.7%, respectively).
The proposed method may significantly contribute to diagnosis and prognosis of pediatric MS.
为了克服儿科多发性硬化症（MS）的诊断困难，需要寻找新的生物标志物。最近，我们开发了一种新的技术，包括脑脊液游离轻链（FLC）单体和二聚体的分析，这可以提高成人 MS 的诊断。本研究旨在评估我们的技术在儿童 MS 诊断中的应用价值。
21 名 MS 患者和 35 名非 MS 脱髓鞘或炎症性神经疾病患者参与了本研究。MS 的诊断基于临床和磁共振成像（MRI）结果。应用 Western blot 分析检测患者 CSF 和血清中的 FLC。评估 FLC 单体和二聚体水平以及 κ/λ 比值的 FLC 指数。还通过寡克隆性测试对样本进行了分析。
研究表明，10 名 MS 患者的 CSF 中κ-FLC 单体和二聚体水平异常升高（“κ 型 MS”）。在 6 名 MS 病例中发现了 λ 二聚体的增加量，而在 3 名 MS 病例中记录了 κ 和 λ FLC 的高水平（“混合型 MS”）。MRI 和临床评估显示“混合”和“λ 型”病例的疾病形式更为侵袭性。与寡克隆性测试相比（分别为 81%和 65.7%），我们的方法在区分 MS 和非 MS 患者方面表现出更高的敏感性（90.5%）和特异性（91.4%）。
该方法可能对儿科 MS 的诊断和预后有重要贡献。
