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接受富马酸二甲酯治疗的复发缓解型多发性硬化症患者的淋巴细胞亚群

Lymphocyte subtypes in relapsing-remitting multiple sclerosis patients treated with dimethyl fumarate.

作者信息

Chaves C, Ganguly R, Ceresia C, Camac A

机构信息

Neurology Department, Lahey Clinic, Lexington, MA, USA.

出版信息

Mult Scler J Exp Transl Clin. 2017 Apr 5;3(2):2055217317702933. doi: 10.1177/2055217317702933. eCollection 2017 Apr-Jun.

DOI:10.1177/2055217317702933
PMID:28607757
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5408504/
Abstract

BACKGROUND

Recent data suggest that lymphopenia is more prevalent than reported in relapsing-remitting multiple sclerosis (RRMS) patients taking dimethyl fumarate (DMF).

OBJECTIVE

The objective of this study was to investigate the effect of DMF on lymphocyte subtypes in RRMS patients with and without lymphopenia.

METHOD

A retrospective study compared lymphocyte subtypes in DMF-treated RRMS patients with low (G1,  = 35) and normal lymphocyte counts (G2,  = 24).

RESULTS

Fifty-nine patients were identified, with mean age 49, 71.2% females, and average DMF duration 20 months. Age, sex, baseline white blood count, disease and treatment durations were similar between groups. Prior interferon therapy and baseline lower normal lymphocyte counts were more frequent in G1. Mean lymphocyte counts were 0.8 ± 0.2 × 10/L in G1 and 1.6 ± 0.3 × 10/L in G2. CD3, CD4, and CD8 T cell mean counts were lower ( < 0.0001), while CD4/CD8 ratio higher ( = 0.03) in G1 than G2. Mean CD19 B cell counts were normal; however, values were lower in G1 ( = 0.04). After adjusting for confounders, significantly positive correlations were noted between lymphocyte counts and CD3 , CD4, CD8 T, and B cell counts. Negative correlation was observed between lymphocyte counts and CD4/CD8 ratio driven by low CD8 T cell counts.

CONCLUSION

DMF treatment predominantly impacts T cells, in particular CD8 subtype. This finding may have implications in this population's immunocompetence.

摘要

背景

近期数据表明,淋巴细胞减少症在服用富马酸二甲酯(DMF)的复发缓解型多发性硬化症(RRMS)患者中比报道的更为普遍。

目的

本研究的目的是调查DMF对有和没有淋巴细胞减少症的RRMS患者淋巴细胞亚群的影响。

方法

一项回顾性研究比较了DMF治疗的淋巴细胞计数低(G1,n = 35)和正常(G2,n = 24)的RRMS患者的淋巴细胞亚群。

结果

共纳入59例患者,平均年龄49岁,女性占71.2%,平均DMF治疗时间20个月。两组之间的年龄、性别、基线白细胞计数、疾病和治疗时间相似。G1组既往干扰素治疗和基线淋巴细胞计数略低于正常更为常见。G1组平均淋巴细胞计数为0.8±0.2×10⁹/L,G2组为1.6±0.3×10⁹/L。G1组的CD3、CD4和CD8 T细胞平均计数较低(P < 0.0001),而CD4/CD8比值较高(P = 0.03)。平均CD19 B细胞计数正常;然而,G1组的值较低(P = 0.04)。在调整混杂因素后,淋巴细胞计数与CD3、CD4、CD8 T细胞和B细胞计数之间存在显著正相关。由于CD8 T细胞计数低,淋巴细胞计数与CD4/CD8比值之间存在负相关。

结论

DMF治疗主要影响T细胞,特别是CD8亚型。这一发现可能对该人群的免疫能力有影响。

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本文引用的文献

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Neurol Neuroimmunol Neuroinflamm. 2015 Dec 10;3(1):e183. doi: 10.1212/NXI.0000000000000183. eCollection 2016 Feb.
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Dimethyl fumarate-associated lymphopenia: Risk factors and clinical significance.富马酸二甲酯相关淋巴细胞减少症:危险因素及临床意义。
Mult Scler J Exp Transl Clin. 2015 Jan-Dec;1. doi: 10.1177/2055217315596994. Epub 2015 Jul 31.
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Dimethyl fumarate selectively reduces memory T cells in multiple sclerosis patients.富马酸二甲酯可选择性减少多发性硬化症患者的记忆性T细胞。
Mult Scler. 2016 Jul;22(8):1061-1070. doi: 10.1177/1352458515608961. Epub 2015 Oct 12.
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PML in Patients Treated with Dimethyl Fumarate.接受富马酸二甲酯治疗患者的进行性多灶性白质脑病
N Engl J Med. 2015 Aug 6;373(6):583-4. doi: 10.1056/NEJMc1506151.
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The effect of dimethyl fumarate (Tecfidera™) on lymphocyte counts: A potential contributor to progressive multifocal leukoencephalopathy risk.富马酸二甲酯(Tecfidera™)对淋巴细胞计数的影响:进行性多灶性白质脑病风险的一个潜在因素。
Mult Scler Relat Disord. 2015 Jul;4(4):377-9. doi: 10.1016/j.msard.2015.05.003. Epub 2015 May 14.
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PML in a patient with lymphocytopenia treated with dimethyl fumarate.一名淋巴细胞减少症患者在接受富马酸二甲酯治疗后发生进行性多灶性白质脑病。
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PML in a patient without severe lymphocytopenia receiving dimethyl fumarate.一名未出现严重淋巴细胞减少的患者在接受富马酸二甲酯治疗时发生进行性多灶性白质脑病。
N Engl J Med. 2015 Apr 9;372(15):1474-6. doi: 10.1056/NEJMc1413724.
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