Peripheral blood T cell dynamics predict relapse in multiple sclerosis patients on fingolimod

Zi Ye Song, Ryo Yamasaki, Yuji Kawano, Shinya Sato, Katsuhisa Masaki, Satoshi Yoshimura, Dai Matsuse, Hiroyuki Murai, Takuya Matsushita, Jun Ichi Kira

研究成果: Contribution to journalArticle査読

42 被引用数 (Scopus)

抄録

Background: 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. Methods/Principal Findings: 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). Conclusions: The CD4+TCM percentages at 2 weeks to 12 months during fingolimod therapy are related to relapse.

本文言語英語
論文番号e0124923
ジャーナルPloS one
10
4
DOI
出版ステータス出版済み - 4 28 2015
外部発表はい

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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