Department of Neurology, University of Ulm, Ulm, Germany.
Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
Front Immunol. 2019 Mar 29;10:641. doi: 10.3389/fimmu.2019.00641. eCollection 2019.
The importance of immunoglobulin G (IgG) oligoclonal bands (OCB) in the diagnosis of multiple sclerosis (MS) was reaffirmed again in the recently revised MS diagnostic criteria. Since OCB testing is based on non-quantitative techniques and demands considerable methodological experience, measurement of CSF immunoglobulin free light chains (FLC) has been suggested as quantitative alternative to OCB. We aimed to establish reference values for FLC measures and evaluate their diagnostic accuracy with regard to the diagnosis of MS. Immunoglobulin kappa (KFLC) and lambda (LFLC) free light chains were prospectively measured by nephelometry in CSF and serum sample pairs in 1,224 patients. The analyzed cohort included patients with MS, other autoimmune or infectious inflammatory diseases of the nervous system as well as 989 patients without signs for nervous system inflammation. Regarding diagnosis of MS, the diagnostic sensitivity and specificity of intrathecal KFLC ratio were 93.3 and 93.7% using the CSF-serum albumin ratio-dependent reference values, 92.0 and 95.9% for intrathecal KFLC ratio applying the ROC-curve determined cut-off levels, 62.7 and 98.3% for IgG index, 64.0 and 98.8% for intrathecal IgG synthesis according to Reiber diagrams, and 94.7 and 93.3% for OCB. Diagnostic sensitivity and specificity of intrathecal LFLC were clearly lower than KFLC. Intrathecal KFLC and OCB showed the highest diagnostic sensitivities for MS. However, specificity was slightly lower compared to other quantitative IgG parameters. Consequently, CSF FLC may not replace OCB, but it may support diagnosis in MS as a quantitative parameter.
免疫球蛋白 G（IgG）寡克隆带（OCB）在多发性硬化症（MS）诊断中的重要性在最近修订的 MS 诊断标准中再次得到肯定。由于 OCB 检测基于非定量技术且需要相当多的方法学经验，因此有人建议测量脑脊液免疫球蛋白游离轻链（FLC）作为 OCB 的定量替代方法。我们旨在建立 FLC 测量的参考值，并评估其在 MS 诊断中的诊断准确性。 通过散射比浊法前瞻性地测量了 1224 例患者脑脊液和血清样本对中的免疫球蛋白κ（KFLC）和 λ（LFLC）游离轻链。分析队列包括 MS 患者、其他自身免疫性或感染性神经系统炎症患者以及 989 例无神经系统炎症迹象的患者。 就 MS 的诊断而言，使用基于 CSF-血清白蛋白比值的参考值，鞘内 KFLC 比值的诊断灵敏度和特异性分别为 93.3%和 93.7%，应用 ROC 曲线确定的截止值时，鞘内 KFLC 比值的诊断灵敏度和特异性分别为 92.0%和 95.9%，IgG 指数的诊断灵敏度和特异性分别为 62.7%和 98.3%，根据 Reiber 图的鞘内 IgG 合成的诊断灵敏度和特异性分别为 64.0%和 98.8%，而 OCB 的诊断灵敏度和特异性分别为 94.7%和 93.3%。鞘内 LFLC 的诊断灵敏度和特异性明显低于 KFLC。 鞘内 KFLC 和 OCB 对 MS 的诊断灵敏度最高。然而，与其他定量 IgG 参数相比，特异性略低。因此，CSF FLC 可能无法替代 OCB，但它可能作为定量参数支持 MS 的诊断。
