Integrative Transcriptomics Uncovers IFN-β Signature and IFITM3 as Putative Molecular Mediator in MS

Neuroinflammation in multiple sclerosis (MS) is driven by the infiltration of myelin-reactive T cells into the central nervous system (CNS). Interferon-β (IFN-β) is one of the earliest disease-modifying treatments (DMTs) approved for MS and remains widely used in special populations (pregnant and elderly patients) owing to its favorable safety profile. However, the exact mechanism of action of this drug and reliable biomarkers of treatment response remain unclear. Transcriptomic profiling and data integration approaches offer powerful tools for investigating complex patterns of regulation and molecular mechanisms underlying therapeutic efficacy. In this study, we performed an integrative analysis of openly available transcriptomic datasets to characterize IFN-β-induced gene expression changes in MS patients. By combining data from large independent cohorts, we identified a 43-gene transcriptional signature consistently associated with IFN-β treatment across disease stages, including progressive MS. To explore the relevance of this signature, we cross-referenced the 43-gene signature with publicly available expression quantitative trait loci (eQTL) datasets to determine whether these genes could be influenced by known MS-associated risk variants highlighting Interferon-Induced Transmembrane Protein 3 (IFITM3) as a candidate molecular mediator of MS. This integrative approach provides new insights into IFN-β-driven immune modulation and supports the development of therapeutic strategies for MS.