Abstract
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.
| Original language | English |
|---|---|
| Article number | e0124923 |
| Journal | PloS one |
| Volume | 10 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 28 2015 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
- General
Cite this
Peripheral blood T cell dynamics predict relapse in multiple sclerosis patients on fingolimod. / Song, Zi Ye; Yamasaki, Ryo; Kawano, Yuji; Sato, Shinya; Masaki, Katsuhisa; Yoshimura, Satoshi; Matsuse, Dai; Murai, Hiroyuki; Matsushita, Takuya; Kira, Jun Ichi.
In: PloS one, Vol. 10, No. 4, e0124923, 28.04.2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Peripheral blood T cell dynamics predict relapse in multiple sclerosis patients on fingolimod
AU - Song, Zi Ye
AU - Yamasaki, Ryo
AU - Kawano, Yuji
AU - Sato, Shinya
AU - Masaki, Katsuhisa
AU - Yoshimura, Satoshi
AU - Matsuse, Dai
AU - Murai, Hiroyuki
AU - Matsushita, Takuya
AU - Kira, Jun Ichi
PY - 2015/4/28
Y1 - 2015/4/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84928692825&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84928692825&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0124923
DO - 10.1371/journal.pone.0124923
M3 - Article
C2 - 25919001
AN - SCOPUS:84928692825
VL - 10
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 4
M1 - e0124923
ER -