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Transcriptomic Analysis of Peripheral Monocytes upon Fingolimod Treatment in Relapsing Remitting Multiple Sclerosis
G Sferruzza1,2, F Clarelli3, E Mascia3
1Department of Neurology, IRCCS San Raffaele Scientific Institute, Via Olgettina, 48, 20132, Milan, Italy.
Molecular Neurobiology
|June 28, 2021
Summary
Fingolimod (FTY) significantly alters monocyte gene expression, primarily down-regulating genes involved in cell activation and migration. Baseline immune gene profiles predict future disease activity in Multiple Sclerosis patients.
Area of Science:
- Immunology
- Neuroscience
- Genomics
Background:
- Fingolimod (FTY) is an oral drug for relapsing remitting Multiple Sclerosis (RRMS), known to prevent lymphocyte migration.
- Evidence suggests FTY also inhibits myeloid cell activation, but its precise mechanism in monocytes requires further elucidation.
Purpose of the Study:
- To investigate the transcriptional changes induced by FTY in monocytes from RRMS patients.
- To identify key pathways and genes affected by FTY treatment.
- To explore the predictive role of baseline monocyte gene expression on treatment response and disease activity.
Main Methods:
- Collected CD14+ monocytes from 24 RRMS patients at baseline and after 6 months of FTY treatment.
- Performed next-generation sequencing for RNA profiling.
- Utilized pathway, sub-path, and centrality analyses on differentially expressed genes (DEGs).
Main Results:
- Observed a significant down-regulation of 60 genes, with no up-regulated genes.
- Down-regulated DEGs were primarily associated with monocyte activation and migration (e.g., IL7R, CCR7, LEF1, TCF7).
- Wnt signaling pathway involvement was confirmed. Baseline expression of HLA-DQA1 and HLA-DPA1 correlated with disease activity after two years.
Conclusions:
- FTY induces substantial transcriptional changes in monocytes, affecting cell trafficking and immune activation.
- Baseline monocyte gene expression, particularly for antigen-presenting genes, can predict long-term disease activity in RRMS patients treated with FTY.

