Soluble TREM-2 in cerebrospinal fluid from patients with multiple sclerosis treated with natalizumab or mitoxantrone
Soluble TREM-2 in cerebrospinal fluid from patients with multiple sclerosis treated with natalizumab or mitoxantrone
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DOI：
10.1177/1352458515624558
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发表时间：
2016-10-01
影响因子：
5.8
通讯作者：
Zetterberg, Henrik
中科院分区：
文献类型：
--
作者：
Ohrfelt, Annika;Axelsson, Markus;Zetterberg, Henrik
背景资料：在髓样细胞-2（TREM-2）上表达的触发受体的小胶质细胞介导的蛋白水解产生可溶性TREM-2（斯特雷姆-2），其可以在脑脊液（CSF）样品中测量。TREM 2或编码其衔接蛋白的基因中的功能缺失突变导致罕见的Nasu-Hakola病（NHD）。多发性硬化症（MS）是一种自身免疫性疾病，与NHD一样以脱髓鞘和小胶质细胞活化为特征，目的：探讨斯特雷姆-2作为MS生物标志物的潜在应用及治疗效果。复发缓解型MS（RRMS）（N = 36）、继发性进展型MS（SPMS）（N = 20）和原发性进展型MS（PPMS）（N = 3）以及对照组（N = 27）。还评估了那他珠单抗或米托蒽醌治疗患者前后CSF中sTREM-2的水平。结果：与对照组相比，RRMS、SPMS和PPMS患者CSF中斯特雷姆-2的水平显著升高。在那他珠单抗处理后，将斯特雷姆-2的水平标准化至对照水平。结论：增加CSF中的斯特雷姆-2水平，小胶质细胞活化的一个新的标志物，在MS和正常化后，无论是那他珠单抗或米托蒽醌治疗后，也降低mitoxantronetreatment.Conclusion的支持小胶质细胞活化的作用，在活跃的MS。
Background: Microglia-mediated proteolysis of the triggering receptor expressed on myeloid cells-2 (TREM-2) produces soluble TREM-2 (sTREM-2) that can be measured in cerebrospinal fluid (CSF) samples. Loss-of-function mutations in TREM2 or in the gene encoding its adaptor protein cause the rare Nasu-Hakola disease (NHD). Multiple sclerosis (MS) is an autoimmune disease that in common with NHD is characterized by demyelination and microglial activation.Objective: To investigate the potential utility of sTREM-2 as a biomarker for MS and to follow treatment effects.Methods: sTREM-2 was analyzed in CSF samples from subjects with MS (N = 59); relapsing-remitting MS (RRMS) (N = 36), secondary progressive MS (SPMS) (N = 20) and primary progressive MS (PPMS) (N = 3), and controls (N = 27). CSF levels of sTREM-2 were also assessed before and after treatment of patients with natalizumab or mitoxantrone.Results: CSF levels of sTREM-2 were significantly increased in patients with RRMS, SPMS, and PPMS compared with controls. After natalizumab treatment, the levels of sTREM-2 were normalized to control levels. The levels of sTREM-2 were also reduced after mitoxantrone treatment.Conclusion: Increased CSF levels of sTREM-2, a new marker of microglial activation, in MS and normalization upon treatment with either natalizumab or mitoxantrone support a role for microglial activation in active MS.