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Transcriptional response to interferon beta-1a treatment in patients with secondary progressive multiple sclerosis

ABSTRACT: Interferon (IFN) beta-1a is an approved treatment for relapsing remitting multiple sclerosis (RRMS) and has been examined for use in secondary progressive multiple sclerosis (SPMS). However, no information regarding blood transcriptional changes induced by IFN treatment in SPMS patients is available. Our aim was to identify a subgroup of SPMS patients presenting a gene expression signature similar to that of RRMS patients who are clinical responders to IFN treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE73608 | GEO | 2015/10/06

SECONDARY ACCESSION(S): PRJNA297802

REPOSITORIES: GEO

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Novel Biomarkers and Interferon Signature in Secondary Progressive Multiple Sclerosis

Project description:Transcriptome analysis of RNA samples from human PBMCs of IFN-beta-1a (Rebif) therapy in secondary progressive multiple sclerosis (SPMS) patients. Objective: Untreated multiple sclerosis is inflammatory, with decreased immune control and subnormal type I interferon (IFN) signaling. IFN-ß therapy corrects abnormal IFN-ß signaling, reduces inflammation on MRI, exacerbations, and disease worsening in relapsing-remitting MS (RRMS). For unclear reasons, secondary progressive MS (SPMS) exhibits waning attacks, relentless neurodegeneration, and diminished benefits of therapy. Methods: Peripheral blood mononuclear cells and serum were from 10 healthy controls (HC), 9 therapy-naive RRMS, 20 therapy-naïve SPMS, and 10 IFN-ß-treated SPMS patients after therapy washout and four hours after IFN-ß-1a injection. Global gene expression was assayed with sensitive RNA microarrays and multiplexed serum immune and neuroprotective protein assays. Results: Therapy-naive RRMS cells displayed 8,723 differentially expressed genes (DEG), compared to HC, vs. d only 3,936 DEG in therapy-naive SPMS. In SPMS, gene expression was subnormal in the WNT/ß-catenin pathway that suppresses inflammation and enhances blood-brain barrier integrity. Olfactory receptor (OR) genes, linked to lymphocyte migration, were overexpressed in RRMS (111 DEG), intermediate in SPMS (34 DEG) vs. HC, differentiating RRMS from SPMS (p < 0.007). IFN-ß injections in SPMS decreased expression of pro-inflammatory genes and increased anti-inflammatory, anti-oxidant metallothionein genes. Pro-inflammatory and anti-inflammatory protein levels were balanced in HC, disrupted in RRMS, and intermediate in SPMS. Interpretation: Aberrant gene expression seen in RRMS wanes in SPMS, paralleling fewer clinical exacerbations and diminished therapeutic responses. Novel biomarkers for SPMS suggest new targets to correct subnormal immune regulation and brain repair in this neurodegenerative disease.

2024-03-07 | GSE247181 | GEO

Defective structural RNA processing in relapsing-remitting multiple sclerosis

Project description:It is fundamentally unknown how normal cellular processes or responses to extracellular stimuli may invoke polyadenylation and degradation of ncRNA substrates or if human disease processes exhibit defects in polyadenylation of ncRNA substrates as part of their pathogenesis. Our results demonstrate that mononuclear cells from subjects with relapsing-remitting multiple sclerosis (RRMS) exhibit pervasive increases in levels of polyadenylated ncRNAs including Y1 RNA, 18S and 28S rRNA, and U1, U2, and U4 snRNAs and these defects are unique to RRMS. Defects in expression of both Ro60 and La proteins in RRMS appear to contribute to increased polyadenylation of ncRNAs. Further, IFN-β1b, a common RRMS therapy, restores both Ro60 and La levels to normal as well as levels of polyadenylated Y1 RNA and U1 snRNA suggesting that aberrant polyadenylation of ncRNA substrates may have pathogenic consequences. We extracted RNA from peripheral whole blood in healthy control subjects and patients with established relapsing-remitting multiple sclerosis using PaxGene tubes.

2015-03-10 | E-GEOD-66573 | biostudies-arrayexpress

Expression data of multiple sclerosis patients receiving Interferon-beta therapy [miRNA-2_0]

Project description:The purpose of this study was to investigate the expression dynamics of mRNAs and microRNAs in response to subcutaneous IFN-beta-1b treatment (Betaferon, 250 µg every other day) in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) or relapsing-remitting type of the disease (RRMS). By using Affymetrix microarrays, we obtained microRNA expression profiles of peripheral blood mononuclear cells from 3 patients within the first month of IFN-beta treatment.

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Expression data of multiple sclerosis patients receiving Interferon-beta therapy [HG-U133_Plus_2]

Project description:The purpose of this study was to investigate the expression dynamics of mRNAs and microRNAs in response to subcutaneous IFN-beta-1b treatment (Betaferon, 250 µg every other day) in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) or relapsing-remitting type of the disease (RRMS). By using Affymetrix microarrays, we obtained gene expression profiles of peripheral blood mononuclear cells from 6 patients within the first month of IFN-beta treatment.

2013-04-24 | GSE46280 | GEO

Expression data of multiple sclerosis patients receiving Interferon-beta therapy [TaqMan(r) Array Human MicroRNA B Cards v2.0]

Project description:The purpose of this study was to investigate the expression dynamics of mRNAs and microRNAs in response to subcutaneous IFN-beta-1b treatment (Betaferon, 250 µg every other day) in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) or relapsing-remitting type of the disease (RRMS). By using TaqMan Array MicroRNA Cards, we obtained microRNA expression profiles of peripheral blood mononuclear cells from 6 patients within the first month of IFN-beta treatment.

2013-04-24 | GSE46292 | GEO

Expression data of multiple sclerosis patients receiving Interferon-beta therapy [TaqMan(r) Array Human MicroRNA A Cards v2.0]

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2013-04-24 | GSE46283 | GEO

Expression data of multiple sclerosis patients receiving intramuscular Interferon-beta-1a therapy [U133 A and B]

Project description:The purpose of this study was to characterize the transcriptional effects induced by intramuscular IFN-beta-1a treatment (Avonex, 30 µg once weekly) in patients with relapsing-remitting form of multiple sclerosis (MS). By using Affymetrix DNA microarrays, we obtained genome-wide expression profiles of peripheral blood mononuclear cells from 24 MS patients within the first four weeks of IFN-beta administration. Keywords: Multiple sclerosis, Interferon, Pharmacogenomics, Affymetrix

2009-12-03 | GSE19285 | GEO

Data in support of Temporal changes of inflammation and endothelial dysfunction in multiple sclerosis related to the evolution of enhancing lesions on frequent brain MRI

Project description:Blood-brain-barrier (BBB) breakdown and active inflammation by relapsing–remitting (RRMS) lesions are hallmarks of multiple sclerosis (MS). Leaky endothelial junctions causes an increased expression of circulating immune cells with associated adhesion molecules on endothelial cell membrane but also an increased production of endothelial derived extracellular microvesicles (EV). Methods: Relapsing–remitting MS (RRMS) patients with no disease-modifying treatment were monitored with weekly intervals using high-resolution 3T MRI scanning. Plasma samples from each measurement were analyzed for protein biomarkers of inflammation by quantitative proteomics, cytokines and chemokines using multiplex immunoassay. Extracellular microvesicles were characterized by an optimized endothelial stress EV Array analysis for detection of soluble secreted microvesicles.

2024-01-26 | PXD035422 | Pride

Alemtuzumab treatment exemplifies discordant immune effects of blood and cerebrospinal fluid in multiple sclerosis

Project description:We here analyzed CSF and blood from two relapsing-remitting multiple sclerosis (RRMS) patients early after peripheral leukocyte depletion with the anti-CD52 antibody alemtuzumab compared to untreated RRMS and control patients using single cell RNA-sequencing.

2023-04-14 | GSE227954 | GEO

Expression data of multiple sclerosis patients receiving subcutaneous Interferon-beta-1a therapy [U133 Plus 2.0]

Project description:The purpose of this study was to characterize the transcriptional effects induced by subcutaneous IFN-beta-1a treatment (Rebif, 22 µg or 44 µg three times a week) in patients with relapsing-remitting form of multiple sclerosis (MS). By using Affymetrix DNA microarrays, we obtained genome-wide expression profiles of peripheral blood mononuclear cells from 12 MS patients within the first two years of IFN-beta administration.

2011-12-06 | GSE33464 | GEO

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