Open AccessTranscriptome profiling of peripheral blood immune cell populations in multiple sclerosis patients before and during treatment with a sphingosine‐1‐phosphate receptor modulator
Author(s) -
Angerer Ines C.,
Hecker Michael,
Koczan Dirk,
Roch Luisa,
Friess Jörg,
Rüge Annelen,
Fitzner Brit,
Boxberger Nina,
Schröder Ina,
Flechtner Kristin,
Thiesen HansJürgen,
Winkelmann Alexander,
Meister Stefanie,
Zettl Uwe K.
Publication year - 2018
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12793
Subject(s) - fingolimod , transcriptome , immune system , multiple sclerosis , microarray , sphingosine , immunology , s1pr1 , receptor , gene expression profiling , biology , medicine , gene expression , cancer research , gene , biochemistry , vascular endothelial growth factor , vascular endothelial growth factor a , vegf receptors
Summary Aims Fingolimod is a sphingosine‐1‐phosphate (S1P) receptor modulator approved for the treatment of the relapsing form of multiple sclerosis ( MS ). It prevents the egress of lymphocyte subpopulations from lymphoid tissues into the circulation. Here, we explored the broad effects of fingolimod on gene expression in different immune cell subsets. Methods Utilizing 150 high‐resolution microarrays from Affymetrix, we obtained the transcriptome profiles of 5 cell populations, which were separated from the peripheral blood of MS patients prior to and following oral administration of fingolimod. Results After 3 months of treatment, significant transcriptome shifts were seen in CD 4+ and CD 8+ cells, which is mainly attributable to the selective homing of naive T cells and central memory T cells. Although the number of B cells was greatly reduced in the blood of fingolimod‐treated MS patients, the analysis of differential expression in CD 19+ cells identified only a small set of 42 genes, which indicated a slightly higher frequency of transitional B cells. The transcriptome signatures of CD 14+ monocytes and CD 56+ natural killer cells were not affected. Conclusion Our study corroborates changes in the composition of circulating immune cells in response to fingolimod and delineates the respective implications at the RNA level. Our data may be valuable for comparing the effects of novel S1P receptor modulating agents, which may be a therapeutic option for patients with secondary progressive MS as well.