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Effective xanthine oxidase inhibitor urate lowering therapy in gout is linked to an emergent serum protein interactome of complement and inflammation modulators
- Source :
- Scientific Reports, Vol 14, Iss 1, Pp 1-11 (2024)
- Publication Year :
- 2024
- Publisher :
- Nature Portfolio, 2024.
-
Abstract
- Abstract Urate-lowering treatment (ULT) to target with xanthine oxidase inhibitors (XOIs) paradoxically causes early increase in gouty arthritis flares. Because delayed reduction in flare burden is mechanistically unclear, we tested for ULT inflammation responsiveness markers. Unbiased proteomics analyzed blood samples (baseline, 48 weeks ULT) in two, independent ULT out trial cohorts (n = 19, n = 30). STRING-db and multivariate analyses supplemented determinations of altered proteins via Wilcoxon matched pairs signed rank testing in XOI ULT responders. Mechanistic studies characterized proteomes of cultured XOI-treated murine bone marrow macrophages (BMDMs). At 48 weeks ULT, serum urate normalized in all gout patients, and flares declined in association with significantly altered proteins (p
- Subjects :
- Xanthine oxidase
Allopurinol
Febuxostat
Gout
Inflammation
Proteomics
Medicine
Science
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 14
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Scientific Reports
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.349f9cade8a437bae5fe3b49312ee3e
- Document Type :
- article
- Full Text :
- https://doi.org/10.1038/s41598-024-74154-5