Peripheral blood T cell dynamics predict relapse in multiple sclerosis patients on fingolimod.
Peripheral blood T cell dynamics predict relapse in multiple sclerosis patients on fingolimod.
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DOI：
10.1371/journal.pone.0124923
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kira J
中科院分区：
文献类型：
--
作者：
Song ZY;Yamasaki R;Kawano Y;Sato S;Masaki K;Yoshimura S;Matsuse D;Murai H;Matsushita T;Kira J
芬戈莫德通过下调1-磷酸鞘氨醇（S1 P）受体抑制淋巴细胞从淋巴结中流出，有效降低多发性硬化（MS）复发。我们的目的是阐明外周血T细胞亚群的变化与MS复发芬戈莫德。通过流式细胞术分析了在芬戈莫德治疗（0.5 mg/天）之前和期间连续收集的23名复发缓解型MS患者和18名健康对照（HC）的血液样本的T细胞亚群。在MS患者中，在芬戈莫德治疗2周至12个月期间，CD 4 +T和CD 8 +T细胞中的中央记忆T（CCR 7 + CD 45 RO+）细胞（TCM）和幼稚T（CCR 7 + CD 45 RO-）细胞的百分比显著降低，而效应记忆T（CCR 7-CD 45 RA-）和抑制性前体T（CD 28-）细胞的百分比均升高。CD 4 +T细胞中调节性T细胞（CD 4 + CD 25 highCD 127 low）和CD 8 +T细胞中CCR 7-CD 45 RA +T细胞的百分比也显著增加。在3个月和6个月时，8名复发患者的CD 4 +TCM百分比高于15名非复发患者（分别为p=0.0051和p=0.0088）。MS患者治疗前产生IL 17、IL 9和IL 4的CD 4 +T细胞百分比显著高于HC患者（所有患者p<0.01），而在芬戈莫德治疗2周时产生IL 17的CD 4 +T细胞百分比倾向于显示一过性增加（pcorr=0.0834）。芬戈莫德治疗2周至12个月时的CD 4 +TCM百分比与复发有关。
Fingolimod efficiently reduces multiple sclerosis (MS) relapse by inhibiting lymphocyte egress from lymph nodes through down-modulation of sphingosine 1-phosphate (S1P) receptors. We aimed to clarify the alterations in peripheral blood T cell subsets associated with MS relapse on fingolimod. Blood samples successively collected from 23 relapsing-remitting MS patients before and during fingolimod therapy (0.5 mg/day) for 12 months and 18 healthy controls (HCs) were analysed for T cell subsets by flow cytometry. In MS patients, the percentages of central memory T (CCR7+CD45RO+) cells (TCM) and naïve T (CCR7+CD45RO-) cells decreased significantly, while those of effector memory T (CCR7-CD45RA-) and suppressor precursor T (CD28-) cells increased in both CD4+T and CD8+T cells from 2 weeks to 12 months during fingolimod therapy. The percentages of regulatory T (CD4+CD25highCD127low) cells in CD4+T cells and CCR7-CD45RA+T cells in CD8+T cells also increased significantly. Eight relapsed patients demonstrated greater percentages of CD4+TCM than 15 non-relapsed patients at 3 and 6 months (p=0.0051 and p=0.0088, respectively). The IL17-, IL9-, and IL4-producing CD4+T cell percentages were significantly higher at pre-treatment in MS patients compared with HCs (p<0.01 for all), while the IL17-producing CD4+T cell percentages tended to show a transient increase at 2 weeks of fingolimod therapy (pcorr=0.0834). The CD4+TCM percentages at 2 weeks to 12 months during fingolimod therapy are related to relapse.
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影响因子：
3.7
作者：
Matsushita T;Tateishi T;Isobe N;Yonekawa T;Yamasaki R;Matsuse D;Murai H;Kira J
通讯作者：
Kira J
影响因子：
5.8
作者：
Min, Ju-Hong;Kim, Byoung Joon;Lee, Kwang Ho
通讯作者：
Lee, Kwang Ho
影响因子：
3.3
作者：
Putheti, P;Soderstrom, M;Huang, YM
通讯作者：
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影响因子：
14.5
作者：
Matsuoka, Takeshi;Matsushita, Takuya;Kira, Jun-ichi
通讯作者：
Kira, Jun-ichi
影响因子：
2.6
作者：
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通讯作者：
Saida T