Patients with multiple sclerosis who develop immunogenicity to interferon-beta have distinct transcriptomic and proteomic signatures prior to treatment which are associated with disease severity
Language English Country United States Media print-electronic
Document type Journal Article
PubMed
39137826
DOI
10.1016/j.clim.2024.110339
PII: S1521-6616(24)00448-0
Knihovny.cz E-resources
- Keywords
- Anti-drug antibodies, Biomarkers, Immunogenicity, Multiple sclerosis, Progression,
- MeSH
- Biomarkers blood MeSH
- Adult MeSH
- Interferon-beta * therapeutic use immunology MeSH
- Middle Aged MeSH
- Humans MeSH
- Proteomics * MeSH
- Multiple Sclerosis, Relapsing-Remitting * drug therapy immunology blood MeSH
- Multiple Sclerosis drug therapy immunology blood MeSH
- Severity of Illness Index MeSH
- Transcriptome * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Biomarkers MeSH
- Interferon-beta * MeSH
Anti-drug antibodies (ADA) reduce the efficacy of immunotherapies in multiple sclerosis (MS) and are associated with increased disease progression risk. Blood biomarkers predicting immunogenicity to biopharmaceuticals represent an unmet clinical need. Patients with relapsing remitting (RR)MS were recruited before (baseline), three, and 12 (M12) months after commencing interferon-beta treatment. Neutralising ADA-status was determined at M12, and patients were stratified at baseline according to their M12 ADA-status (ADA-positive/ADA-negative). Patients stratified as ADA-positive were characterised by an early dampened response to interferon-beta (prior to serum ADA detection) and distinct proinflammatory transcriptomic/proteomic peripheral blood signatures enriched for 'immune response activation' including phosphoinositide 3-kinase-γ and NFκB-signalling pathways both at baseline and throughout the treatment course, compared to ADA-negative patients. These immunogenicity-associated proinflammatory signatures significantly overlapped with signatures of MS disease severity. Thus, whole blood molecular profiling is a promising tool for prediction of ADA-development in RRMS and could provide insight into mechanisms of immunogenicity.
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