Department of Neurology, Medical University of Graz, Graz, Austria.
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
Mult Scler. 2017 Oct;23(11):1496-1505. doi: 10.1177/1352458516681503. Epub 2016 Nov 29.
Cerebrospinal fluid (CSF) immunoglobulin free light chains (FLC) have been suggested as quantitative alternative to oligoclonal bands (OCB) in the diagnosis of multiple sclerosis (MS). However, little is known on their role in predicting clinical and paraclinical disease progression, particularly in early stages.
To assess the prognostic value of FLC in OCB-positive patients with clinically isolated syndrome (CIS) suggestive of MS and early MS.
We determined FLC kappa (KFLC) and lambda (LFLC) in CSF and serum by nephelometry in 61 patients (CIS ( n = 48), relapsing-remitting multiple sclerosis ( n = 13)) and 60 non-inflammatory neurological controls. Median clinical follow-up time in CIS was 4.8 years (interquartile range (IQR), 1.5-6.5 years). Patients underwent 3T magnetic resonance imaging (MRI) at baseline and follow-up (median time interval, 2.2 years; IQR, 1.0-3.7 years) to determine T2 lesion load (T2LL) and percent brain volume change (PBVC).
CSF FLC were significantly increased in CIS/MS compared to controls (all p < 0.001). A lower KFLC/LFLC CSF ratio was associated with CIS-clinically definite multiple sclerosis (CDMS) conversion (hazard ratio (HR) = 2.89; 95% confidence interval (CI) = 1.17-7.14; p < 0.05). No correlations were found for FLC variables with T2LL or PBVC.
Our study confirms increased intrathecal synthesis of FLC in CIS/MS which supports their diagnostic contribution. The KFLC/LFLC CSF ratio appears to have a prognostic value in CIS beyond OCB.
脑脊液(CSF)免疫球蛋白游离轻链(FLC)已被提议作为多发性硬化症(MS)诊断中寡克隆带(OCB)的定量替代物。然而,关于它们在预测临床和临床前疾病进展中的作用,特别是在早期阶段,知之甚少。
评估 FLC 在 OCB 阳性、临床孤立综合征(CIS)提示 MS 和早期 MS 患者中的预后价值。
我们通过散射比浊法在 61 例患者(CIS(n=48)、复发缓解型多发性硬化症(n=13))和 60 例非炎症性神经学对照者的 CSF 和血清中测定 K 型 FLC(KFLC)和 λ 型 FLC(LFLC)。CIS 患者的中位临床随访时间为 4.8 年(四分位距(IQR),1.5-6.5 年)。患者在基线和随访时进行 3T 磁共振成像(MRI)检查(中位时间间隔为 2.2 年;IQR,1.0-3.7 年),以确定 T2 病变负荷(T2LL)和脑容量变化百分比(PBVC)。
与对照组相比,CIS/MS 患者的 CSF FLC 显著升高(均 p<0.001)。较低的 KFLC/LFLC CSF 比值与 CIS-临床确诊多发性硬化症(CDMS)转化相关(危险比(HR)=2.89;95%置信区间(CI)=1.17-7.14;p<0.05)。FLC 变量与 T2LL 或 PBVC 之间无相关性。
我们的研究证实 CIS/MS 患者的 CSF 中 FLC 合成增加,这支持了其诊断贡献。KFLC/LFLC CSF 比值在 CIS 中除了 OCB 之外,似乎具有预后价值。