Makshakov G S, Nazarov V D, Totolyan N A, Lapin S V, Mazing A V, Emanuel V L, Krasnov V S, Shumilina M V, Skoromets A A, Evdoshenko E P
City Center of Multiple Sclerosis and Other Autoimmune Diseases, City Clinical Hospital #31, St. Petersburg, Russia; Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia.
Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia.
Zh Nevrol Psikhiatr Im S S Korsakova. 2017;117(10. Vyp. 2):4-10. doi: 10.17116/jnevro20171171024-10.
To assess an impact of immunoglobulin free light chains (FLC) on short-term and long-term prognosis of clinical and radiological activity and progression of disability in multiple sclerosis (MS).
A sample of 381 patients with definite MS was divided into 2 groups. In group 1, lumbar puncture was performed at the time of clinically isolated syndrome, and patients were prospectively followed up to 2 years (short-term prognosis group, n=97). In group 2, MS was diagnosed immediately after lumbar puncture, and retrospective analysis of the disease course with the duration not less than 5 years was performed (long-term prognosis group, n=284). The Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS) were used to assess patient's status. Concentrations of kappa and lambda FLC in the CSF (K-FLC, L-FLC) and serum (K-FLC, L-FLC) as well as quotients of concentrations (Q-K and Q-L) were determined. Patients were stratified into subgroups with high and low concentrations of K-FLC and L-FLC using cut-offs from our previous studies: K-FLC=0.595 mcg/l and L-FLC=0.127 mcg/l.
In group 1, significant correlations were found only between EDSS score and concentrations of K-FLC (r=0.377, p=0.00019) and Q-K (r=0.366, p=0.0012). FLC concentrations did not correlate with the number of relapses and new T2 lesions. The age and EDSS score at the disease onset didn't differ between patients with high and low K-FLC and L-FLC (K-FLC: р=0.2658; L-FLC: р=0.5502). A significant decrease of EDSS score after the disease onset was observed in all groups except for patients with high concentrations of K-FLC (p=0.1844), so the EDSS score after 2 years was significantly higher in this subgroup of patients (p=0.0006). In group 2, significant correlations of K-FLC with EDSS score (r=0.181, p=0.002) and MSSS score (r=0.121, р=0.044) for long-term prognosis (median (IQR) = 8 (6-13) years) were found. No correlations of FLC concentrations with the number of relapses during the first 5 years were found. Survival analysis showed that high concentrations of K-FLC were associated with the high risk of progression to EDSS 6 (HR=2.055, p=0.026) but not with EDSS 4 (HR=2.388, p=0.08).
Concentrations of kappa FLC can help to define the prognosis of MS early at the disease course. Although low concentrations of FLC do not exclude a severe disease phenotype, patients with high K-FLC concentrations are at greater risk for faster MS progression, probably, due to impaired reparation of neural tissue. Measurement of FLC concentrations can be used to determine a therapeutic tactics in patients with MS.
评估免疫球蛋白游离轻链（FLC）对多发性硬化症（MS）临床和放射学活动以及残疾进展的短期和长期预后的影响。
381例确诊为MS的患者样本被分为2组。第1组在临床孤立综合征时进行腰椎穿刺，并对患者进行前瞻性随访2年（短期预后组，n = 97）。第2组在腰椎穿刺后立即诊断为MS，并对病程不少于5年的患者进行回顾性分析（长期预后组，n = 284）。采用扩展残疾状态量表（EDSS）和多发性硬化症严重程度评分（MSSS）评估患者状况。测定脑脊液（K-FLC、L-FLC）和血清（K-FLC、L-FLC）中κ和λFLC的浓度以及浓度商（Q-K和Q-L）。根据我们之前研究的临界值：K-FLC = 0.595 mcg/l和L-FLC = 0.127 mcg/l，将患者分层为K-FLC和L-FLC浓度高和低的亚组。
在第1组中，仅发现EDSS评分与K-FLC浓度（r = 0.377，p = 0.00019）和Q-K（r = 0.366，p = 0.0012）之间存在显著相关性。FLC浓度与复发次数和新的T2病变数量无关。K-FLC和L-FLC浓度高和低的患者在疾病发作时的年龄和EDSS评分无差异（K-FLC：p = 0.2658；L-FLC：p = 0.5502）。除K-FLC浓度高的患者外，所有组在疾病发作后EDSS评分均显著下降（p = 0.1844），因此该亚组患者2年后的EDSS评分显著更高（p = 0.0006）。在第2组中，发现K-FLC与长期预后（中位数（IQR）= 8（6 - 13）年）的EDSS评分（r = 0.181，p = 0.002）和MSSS评分（r = 0.121，p = 0.044）存在显著相关性。未发现FLC浓度与前5年复发次数之间的相关性。生存分析表明，高浓度的K-FLC与进展至EDSS 6的高风险相关（HR = 2.055，p = 0.026），但与EDSS 4无关（HR = 2.388，p = 0.08）。
κFLC浓度有助于在疾病进程早期确定MS的预后。虽然低浓度的FLC并不排除严重的疾病表型，但K-FLC浓度高的患者MS进展更快的风险更大，可能是由于神经组织修复受损。FLC浓度的测量可用于确定MS患者的治疗策略。
