Rheumatoid arthritis

Phosphoproteomic profiling of early rheumatoid arthritis synovium reveals active signalling pathways and differentiates inflammatory pathotypes

Arthritis Res TherPublished Mechanistic study

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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