自体造血干细胞移植治疗多发性硬化症后，脱髓鞘和轴突损伤的生物标志物减少。
Biomarkers of demyelination and axonal damage are decreased after autologous hematopoietic stem cell transplantation for multiple sclerosis.
作者信息
Zjukovskaja Christina, Larsson Anders, Cherif Honar, Kultima Kim, Burman Joachim
机构信息
Department of Medical Sciences, Uppsala University, Uppsala SE-751 85, Sweden.
Department of Medical Sciences, Uppsala University, Uppsala SE-751 85, Sweden.
出版信息
Mult Scler Relat Disord. 2022 Dec;68:104210. doi: 10.1016/j.msard.2022.104210. Epub 2022 Oct 3.
BACKGROUND
Autologous hematopoietic stem cell transplantation (aHSCT) has seen increased use for relapsing-remitting multiple sclerosis (RRMS) in recent years. It is considered one of the most effective treatments for RRMS and has been associated with improvement in disability and prolonged remission. This suggests that the tissue-injuring disease process may have been altered by aHSCT. To assess whether this hypothesis is correct, we performed a study of three commonly used cerebrospinal fluid biomarkers of tissue damage.
METHODS
In this single center study, 63 patients treated with aHSCT at Uppsala University Hospital between January 1st 2012 and January 31st 2019 were screened for participation. A control group consisting of volunteers without neurologic disease were included as a reference. Cerebrospinal fluid concentrations of neurofilament light (NFL), myelin basic protein (MBP) and glial acidic fibrillary protein (GFAp) were determined using ELISA and a multiplex proteomics platform from Meso Scale Discovery.
RESULTS
Forty-three patients with a mean age of 31 and a median follow-up time of 3.9 years were included. Their median baseline expanded disability status scale (EDSS) score was 3.5 and the annualized relapse rate in the year preceding aHSCT was 1.6. At baseline the proportion of patients with values above the upper limit of normal was 67% for NFL, 63% for MBP and 16% for GFAp. At 5-year follow-up, the proportion of patients with values above the upper limit of normal was 12% for NFL, 12% for MBP and 25% for GFAp. The mean concentration of NFL decreased from 920 pg/mL at baseline to 270 pg/mL at 5-year follow-up (p < 0.001); MBP decreased from 1500 to 680 pg/mL (p < 0.001); whereas the mean concentration of GFAp was unchanged.
CONCLUSION
In a majority of patients, biomarkers of demyelination and axonal damage reached normal values within five years from treatment with aHSCT.
背景
近年来，自体造血干细胞移植（aHSCT）在复发缓解型多发性硬化症（RRMS）中的应用有所增加。它被认为是RRMS最有效的治疗方法之一，与残疾改善和缓解期延长有关。这表明组织损伤性疾病进程可能已被aHSCT改变。为评估这一假设是否正确，我们对三种常用的组织损伤脑脊液生物标志物进行了研究。
方法
在这项单中心研究中，对2012年1月1日至2019年1月31日期间在乌普萨拉大学医院接受aHSCT治疗的63例患者进行了参与筛查。包括一组无神经系统疾病的志愿者作为对照组。使用酶联免疫吸附测定（ELISA）和Meso Scale Discovery的多重蛋白质组学平台测定脑脊液中神经丝轻链（NFL）、髓鞘碱性蛋白（MBP）和胶质纤维酸性蛋白（GFAp）的浓度。
结果
纳入了43例患者，平均年龄31岁，中位随访时间3.9年。他们的基线扩展残疾状态量表（EDSS）中位评分为3.5，aHSCT前一年的年化复发率为1.6。基线时，NFL值高于正常上限的患者比例为67%，MBP为63%，GFAp为16%。在5年随访时，NFL值高于正常上限的患者比例为12%，MBP为12%，GFAp为25%。NFL的平均浓度从基线时的920 pg/mL降至5年随访时的270 pg/mL（p < 0.001）；MBP从1500降至680 pg/mL（p < 0.001）；而GFAp的平均浓度未改变。
结论
在大多数患者中，脱髓鞘和轴突损伤的生物标志物在接受aHSCT治疗后的五年内达到正常水平。
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