Fingolimod alters the transcriptome profile of circulating CD4+ cells in multiple sclerosis.
Multiple sclerosis is a demyelinating disease affecting the central nervous system. T cells are known to contribute to this immune-mediated condition. Fingolimod modulates sphingosine-1-phosphate receptors, thereby preventing the egress of lymphocytes, especially CCR7-expressing CD8+ and CD4+ T cells, from lymphoid tissues. Using Affymetrix Human Transcriptome Arrays (HTA 2.0), we performed a transcriptome profiling analysis of CD4+ cells obtained from the peripheral blood of patients with highly active relapsing-remitting multiple sclerosis. The samples were drawn before the first administration of fingolimod as well as 24 hours and 3 months after the start of therapy. Three months after treatment initiation, 890 genes were found to be differentially expressed with fold-change >2.0 and t-test p-value < 0.001, among them several microRNA precursors. A subset of 272 genes were expressed at lower levels, including CCR7 as expected, while 618 genes showed an increase in expression, e.g., CCR2, CX3CR1, CD39, CD58 as well as LYN, PAK1 and TLR2. To conclude, we studied the gene expression of CD4+ cells to evaluate the effects of fingolimod treatment, and we identified 890 genes to be altered in expression after continuous drug administration. T helper cells circulating in the blood during fingolimod therapy present a distinct gene expression signature.
University of Rostock, Department of Neurology, Division of Neuroimmunology, Gehlsheimer Str. 20, 18147 Rostock, Germany.
Jörg
J
Friess
University of Rostock, Department of Neurology, Division of Neuroimmunology, Gehlsheimer Str. 20, 18147 Rostock, Germany.|Steinbeis Transfer Centre for Proteome Analysis, Schillingallee 70, 18057 Rostock, Germany.
Michael
M
Hecker
University of Rostock, Department of Neurology, Division of Neuroimmunology, Gehlsheimer Str. 20, 18147 Rostock, Germany.
Luisa
L
Roch
Steinbeis Transfer Centre for Proteome Analysis, Schillingallee 70, 18057 Rostock, Germany.|University of Rostock, Institute of Immunology, Schillingallee 70, 18057 Rostock, Germany.
Dirk
D
Koczan
Steinbeis Transfer Centre for Proteome Analysis, Schillingallee 70, 18057 Rostock, Germany.
Brit
B
Fitzner
University of Rostock, Department of Neurology, Division of Neuroimmunology, Gehlsheimer Str. 20, 18147 Rostock, Germany.
Ines Charlotte
IC
Angerer
University of Rostock, Department of Neurology, Division of Neuroimmunology, Gehlsheimer Str. 20, 18147 Rostock, Germany.
Ina
I
Schröder
University of Rostock, Institute of Immunology, Schillingallee 70, 18057 Rostock, Germany.
Kristin
K
Flechtner
Steinbeis Transfer Centre for Proteome Analysis, Schillingallee 70, 18057 Rostock, Germany.|University of Rostock, Institute of Immunology, Schillingallee 70, 18057 Rostock, Germany.
Hans-Jürgen
HJ
Thiesen
University of Rostock, Department of Neurology, Division of Neuroimmunology, Gehlsheimer Str. 20, 18147 Rostock, Germany.
Alexander
A
Winkelmann
University of Rostock, Department of Neurology, Division of Neuroimmunology, Gehlsheimer Str. 20, 18147 Rostock, Germany.
Uwe Klaus
UK
Zettl
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D059467:Transcriptome
D007166:Immunosuppressive Agents; D000068876:Fingolimod Hydrochloride