Novel Biomarkers and Interferon Signature in Secondary Progressive Multiple Sclerosis
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ABSTRACT:
PROVIDER: PRJNA1036589 | ENA |
REPOSITORIES: ENA
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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
Project description: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.
2015-10-06 | GSE73608 | GEO
Project description:Multiple Sclerosis is a complex neurological disorder characterised by inflammation, demyelination, and neurodegeneration of the central nervous system. While treatments exist for relapsing-remitting multiple sclerosis, therapeutic options for the progressive forms remain limited, highlighting the need to understand their distinct pathological mechanisms. To identify subtype specific molecular signatures in patients with multiple sclerosis, bulk RNA sequencing was performed in 90 brain tissue samples from donors with relapsing-remitting, secondary progressive, and primary progressive multiple sclerosis, as well as controls without the disease. This study provides open access to transcriptomic data from multiple sclerosis tissue samples, enabling other researchers to perform independent analyses, validate findings, and generate new hypotheses.
2025-02-26 | GSE290450 | GEO
Project description:Multiple Sclerosis is a complex neurological disorder characterised by inflammation, demyelination, and neurodegeneration of the central nervous system. While treatments exist for relapsing-remitting multiple sclerosis, therapeutic options for the progressive forms remain limited, highlighting the need to understand their distinct pathological mechanisms. To identify subtype specific molecular signatures in patients with multiple sclerosis, bulk RNA sequencing was performed in 90 brain tissue samples from donors with relapsing-remitting, secondary progressive, and primary progressive multiple sclerosis, as well as controls without the disease. This study provides open access to transcriptomic data from multiple sclerosis tissue samples, enabling other researchers to perform independent analyses, validate findings, and generate new hypotheses.
2025-02-26 | GSE290552 | GEO
Project description:Progressive multiple sclerosis
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Project description:Siponimod selectively enriched regulatory T and B lymphocytes in active secondary progressive multiple sclerosis patients: 20 SPMS baseline including 3 repeats, 19 treated with 5 placebo and 14 siponimod treated.
2020-04-07 | GSE141381 | GEO
Project description:Mapping the Molecular Signature of Progressive Multiple Sclerosis
| PRJNA1228601 | ENA
Project description:Objective: Progression in multiple sclerosis (MS) often corresponds to irreversible disability in MS patients. Cellular changes in the cerebrospinal fluid (CSF) have provided biomarkers and mechanisms in relapsing-remitting MS (RRMS) but remain understudied in primary and secondary progressive MS (summarized herein as PMS). Methods: We combined retrospective flow cytometry of CSF cells from RRMS (n = 169), PMS (n = 56), and non-inflammatory controls (n = 74) with prospective CSF single-cell transcriptomics of 35 individuals (11 controls, 12 RRMS, and 12 PMS) and with confirmatory CSF ELISA. Available CSF single cell data from age-matched and Alzheimer’s disease served as additional controls. Results: Proportions of CD14+ monocytes in CSF are increased in PMS and correlated with clinical surrogate markers of progression. Transcriptionally, these monocytes resembled border-associated macrophages (BAM)-like cells with a chronically activated antigen-presenting phenotype. Additionally, these monocytes shared some features with disease-associated microglia/macrophages (DAM), previously identified in neurodegeneration. Induction of DAM-associated molecules, including transcribed and soluble TREM2, was unique to SPMS and supported its differential diagnosis. Interpretation: We thus identified MS stage-specific CSF signatures and shared cellular features of degeneration detectable in CSF of PMS patients.
2026-05-17 | GSE328264 | GEO
Project description:Objective: Progression in multiple sclerosis (MS) often corresponds to irreversible disability in MS patients. Cellular changes in the cerebrospinal fluid (CSF) have provided biomarkers and mechanisms in relapsing-remitting MS (RRMS) but remain understudied in primary and secondary progressive MS (summarized herein as PMS). Methods: We combined retrospective flow cytometry of CSF cells from RRMS (n = 169), PMS (n = 56), and non-inflammatory controls (n = 74) with prospective CSF single-cell transcriptomics of 35 individuals (11 controls, 12 RRMS, and 12 PMS) and with confirmatory CSF ELISA. Available CSF single cell data from age-matched and Alzheimer’s disease served as additional controls. Results: Proportions of CD14+ monocytes in CSF are increased in PMS and correlated with clinical surrogate markers of progression. Transcriptionally, these monocytes resembled border-associated macrophages (BAM)-like cells with a chronically activated antigen-presenting phenotype. Additionally, these monocytes shared some features with disease-associated microglia/macrophages (DAM), previously identified in neurodegeneration. Induction of DAM-associated molecules, including transcribed and soluble TREM2, was unique to SPMS and supported its differential diagnosis. Interpretation: We thus identified MS stage-specific CSF signatures and shared cellular features of degeneration detectable in CSF of PMS patients.
2026-05-17 | GSE327243 | GEO
Project description:Mapping the Molecular Signature of Progressive Multiple Sclerosis [194017]
| PRJNA1228055 | ENA