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
N1 - Funding Information:
Jun-ichi Kira serves as an editorial board member of Clinical and Experimental Neuroimmunology, Multiple Sclerosis Journal, Multiple Sclerosis and Related Disorders, BMC Medicine, PLOS ONE, Expert Review of Neurotherapeutics, Intractable and Rare Diseases Research, The Scientific World Journal, and Journal of the Neurological Sciences. The authors have received support from the following commercial sources: Bayer Schering Pharma, Biogen Idec, Novartis Pharma, Mitsubishi Tanabe Pharma, Pfizer, and the Japan Blood Products Organization. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
Publisher Copyright:
© 2015 Song et al.
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.
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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 -