Characteristic cerebrospinal fluid cytokine/chemokine profiles in neuromyelitis optica, relapsing remitting or primary progressive multiple sclerosis.

Characteristic cerebrospinal fluid cytokine/chemokine profiles in neuromyelitis optica, relapsing remitting or primary progressive multiple sclerosis.
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DOI:
10.1371/journal.pone.0061835
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Kira J
Kira J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Matsushita T;Tateishi T;Isobe N;Yonekawa T;Yamasaki R;Matsuse D;Murai H;Kira J

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视神经脊髓炎(NMO)、复发缓解型多发性硬化症(RRMS)和原发性进行性多发性硬化症(PPMS)患者中细胞因子/趋化因子谱的差异,以及这些谱与临床和神经影像学特征的关系尚不清楚。更好地了解这些特征可能有助于鉴别诊断。我们用多路荧光珠免疫分析法检测了20例NMO患者、26例RRMS患者、9例PPMS患者和18例其他非炎症性神经疾病(OND)患者脑脊液中的27种细胞因子/趋化因子和生长因子。复发时NMO患者的白细胞介素(IL)-17A、IL-6、CXCL8、CXCL10水平明显高于OND和RRMS患者,而NMO患者的粒细胞集落刺激因子(G-CSF)、CCL4水平明显高于OND患者。在NMO患者中,IL-6和CXCL8水平与残疾和CSF蛋白浓度呈正相关,而IL-6、CXCL8、G-CSF、粒细胞-巨噬细胞集落刺激因子(GM-CSF)和IFN-γ与采集样本时CSF中性粒细胞计数呈正相关。RRMS患者复发期IL-6水平明显高于OND患者,脑脊液细胞计数与CCL2水平呈负相关。复发期细胞因子/趋化因子在三种组合(IL-6与GM-CSF、G-CSF与GM-CSF、GM-CSF与IFN-γ)中与RRMS和NMO/NMOSD患者的相关系数有显著差异。PPMS患者CCL4和CXCL10水平明显高于OND患者。我们的研究结果表明,NMO、RRMS和PPMS患者脑脊液中存在不同的细胞因子/趋化因子改变。在NMO中,Th17-和th1相关的促炎细胞因子/趋化因子簇的过度表达是特征性的,而在PPMS中,CCL4和CXCL10水平的升高可能反映了中枢神经系统中持续的低级别T细胞和巨噬细胞/小胶质细胞炎症。在RRMS中,复发时仅检测到促炎细胞因子/趋化因子的轻度升高。
Differences in cytokine/chemokine profiles among patients with neuromyelitis optica (NMO), relapsing remitting multiple sclerosis (RRMS), and primary progressive MS (PPMS), and the relationships of these profiles with clinical and neuroimaging features are unclear. A greater understanding of these profiles may help in differential diagnosis. We measured 27 cytokines/chemokines and growth factors in CSF collected from 20 patients with NMO, 26 with RRMS, nine with PPMS, and 18 with other non-inflammatory neurological diseases (OND) by multiplexed fluorescent bead-based immunoassay. Interleukin (IL)-17A, IL-6, CXCL8 and CXCL10 levels were significantly higher in NMO patients than in OND and RRMS patients at relapse, while granulocyte-colony stimulating factor (G-CSF) and CCL4 levels were significantly higher in NMO patients than in OND patients. In NMO patients, IL-6 and CXCL8 levels were positively correlated with disability and CSF protein concentration while IL-6, CXCL8, G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-γ were positively correlated with CSF neutrophil counts at the time of sample collection. In RRMS patients, IL-6 levels were significantly higher than in OND patients at the relapse phase while CSF cell counts were negatively correlated with the levels of CCL2. Correlation coefficients of cytokines/chemokines in the relapse phase were significantly different in three combinations, IL-6 and GM-CSF, G-CSF and GM-CSF, and GM-CSF and IFN-γ, between RRMS and NMO/NMOSD patients. In PPMS patients, CCL4 and CXCL10 levels were significantly higher than in OND patients. Our findings suggest distinct cytokine/chemokine alterations in CSF exist among NMO, RRMS and PPMS. In NMO, over-expression of a cluster of Th17- and Th1-related proinflammatory cytokines/chemokines is characteristic, while in PPMS, increased CCL4 and CXCL10 levels may reflect on-going low grade T cell and macrophage/microglia inflammation in the central nervous system. In RRMS, only a mild elevation of proinflammatory cytokines/chemokines was detectable at relapse.
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