Dataset Information

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

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.

SUBMITTER: Song ZY

PROVIDER: S-EPMC4412716 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

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

Song Zi-Ye ZY Yamasaki Ryo R Kawano Yuji Y Sato Shinya S Masaki Katsuhisa K Yoshimura Satoshi S Matsuse Dai D Murai Hiroyuki H Matsushita Takuya T Kira Jun-ichi J

PloS one 20140101 4

<h4>Background</h4>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.<h4>Methods/principal findings</h4>Blood samples successively collected from 23 relapsing-remitting MS patients before and during fingolimod therapy (0.5 mg/day) for 12 months and 18 health ...[more]

PMID: 25919001

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Project description:BACKGROUND:Fingolimod is a once-daily, orally administered therapy for relapsing forms of MS. It has been shown to reduce relapse rates significantly in all phase II and phase III clinical trials when compared with placebo and intramuscular interferon ?-1a (IFN?-1a IM). METHODS:This study compared annualized relapse rates (ARRs) associated with fingolimod, placebo and IFN?-1a IM, in patient subgroups from the pooled FREEDOMS, FREEDOMS II, and TRANSFORMS populations. This provided a large data set in which the efficacy of fingolimod could be assessed across a range of patient subgroups, including clinically relevant subgroups not previously analysed. RESULTS:Compared with placebo, fingolimod was associated with significantly lower ARRs across all patient subgroups with relative reductions in ARRs ranging from 35% (patients who had previously received treatment for their MS for up to 1 year; P<0.05) to 69% (patients with symptoms for less than 3 years before study entry; P<0.001). Other relative reductions in ARR compared with placebo included 64% in patients aged 40 years or younger and 63% in those naïve to treatment (P<0.001 for both). Compared with IFN?-1a IM, the greatest benefits to ARR were seen in patients aged 40 years or younger (55% relative ARR reduction, P<0.001) and in a small subgroup of patients who had previously received IFN? and glatiramer acetate (55% relative ARR reduction; P<0.05). Reductions in ARR compared with IFN?-1a IM were not statistically significant in men (33%, P=0.081), in patients aged over 40 years (23%, P=0.230) and in those who had received treatment prior to the study for 1 year or less (35%, P=0.108). Fingolimod was associated with significantly lower ARRs compared with placebo and with IFN?-1a IM irrespective of treatment status (treatment-naïve and previously treated for MS), and regardless of type of previous therapy. CONCLUSIONS:Fingolimod provided consistent efficacy benefits over placebo and IFN?-1a IM across a range of subgroups of patients with relapsing MS. The magnitude of the beneficial effect of fingolimod over IFN?-1a IM may depend on age, sex, and duration of previous treatment. These findings suggest that most benefit will be gained by patients who start fingolimod early in the disease course, but the findings also suggest that fingolimod treatment will benefit patients later in the disease course when they have already accrued disability.

Dataset Information

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

Background

Methods/principal findings

Conclusions

Publications

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

Similar Datasets

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