Analysis of coding and non-coding transcriptome of peripheral B cells reveals an altered interferon response factor (IRF)-1 pathway in multiple sclerosis patients.

Abstract Several evidences emphasize B-cell pathogenic roles in multiple sclerosis (MS). We performed transcriptome analyses on peripheral B cells from therapy-free patients and age/sex-matched controls. Down-regulation of two transcripts (interferon response factor 1–IRF1, and C-X-C motif chemokine 10–CXCL10), belonging to the same pathway, was validated by RT-PCR in 26 patients and 21 controls. IRF1 and CXCL10 transcripts share potential seeding sequences for hsa-miR-424, that resulted up-regulated in MS patients. We confirmed this interaction and its functional effect by transfection experiments. Consistent findings indicate down-regulation of IRF1/CXCL10 axis, that may plausibly contribute to a pro-survival status of B cells in MS. Graphical abstract Unlabelled Image Highlights • Interferon response factor 1 and C-X-C motif chemokine 10 were down-regulated in MS. • The altered gene expression was possibly driven by a shared regulatory miRNA. • Both transcript shared a potential seeding sequences for has-miR-424. • Hsa-miR-424 was among up-regulated micro-RNAs in peripheral B cells from patients. • Hsa-miR-424-IRF1 mRNA interaction had functional effects at transfection experiments. [ABSTRACT FROM AUTHOR]