Phosphoproteomic profiling of early rheumatoid arthritis synovium reveals active signalling pathways and differentiates inflammatory pathotypes
Authors' conclusion
Specific phosphoproteome/proteome signatures delineate RA pathotypes
Study context
- Population
- Treatment-naive rheumatoid arthritis (RA) patients; pre-treatment synovial biopsies
- Participants
- 8 synovial biopsies
- Comparison
- Lymphoid vs myeloid RA pathotypes
Methodological detailslabel-free mass spectrometry, phosphoproteome and total proteome analysis
- Label-free mass spectrometry
- Phosphoproteome and total proteome analysis
Main finding
As reported in the abstract
- Clear separation of phosphoproteome and proteome profiles between lymphoid and myeloid RA pathotypes
- Abundance of specific phosphosites associated with degree of inflammatory state
- Lymphoid pathotype enriched with lymphoproliferative signalling phosphosites, incl. Mammalian Target Of Rapamycin (MTOR) signalling
- Myeloid pathotype associated with Mitogen-Activated Protein Kinase (MAPK) and CDK mediated signalling
- Novel kinases not previously linked to RA, e.g. PRKDC in myeloid pathotype
- Several phosphosites correlated with clinical features, e.g. DAS28
Original publication
Phosphoproteomic profiling of early rheumatoid arthritis synovium reveals active signalling pathways and differentiates inflammatory pathotypes. Arthritis Res Ther. Published 12 June 2024. doi:10. 1186/ s13075-024-03351-4
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