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PXD044963-1

PXD044963 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePhosphoproteomic profiling discriminates between myeloid and lymphoid pathotypes in early RA synovium
DescriptionBackground: Rheumatoid arthritis (RA) is a complex heterogenous autoimmune disease and achieving long term disease remission is an elusive goal for patients, thus implying improvement in drug targeting is necessary. Kinases are intracellular signalling mediators and key to sustaining the inflammatory process in RA. Therefore, oral inhibitors of specific kinases, such as Cyclin Dependent Kinases (CDKs) and Janus Kinase (JAKs), are under development or have been approved. However, the cell signalling mechanisms in treatment naïve RA patients is yet to be explored, which may facilitate targeted therapy stratification. Methods: We undertook phosphoproteome and total proteome analysis of 8 pre-treatment synovial biopsies of RA patients using label-free mass spectrometry. Results: The analysis revealed a clear separation of the phosphoproteome and proteome profile between the lymphoid and myeloid RA pathotypes. Differential expression analysis and function enrichment showed that the degree of inflammatory state and specific signalling activities are associated with different RA pathotypes. The lymphoid pathotype was enriched with immunological pathways and associated with Mammalian Target Of Rapamycin (MTOR) signalling, whereas the myeloid pathotype was associated with Mitogen-Activated Protein Kinase (MAPK) and CDK mediated signalling. This analysis also highlighted kinases not previously linked to RA, such as Serine/Threonine Protein Kinase N1 (PKN1) in the lymphoid pathotype and Protein Kinase, DNA-Activated, Catalytic Subunit (PRKDC) in the myeloid pathotypes. Certain phosphosites were also highly correlated with clinical features, such as Disabled Homolog 2 (DAB2)-Ser723 with Disease Activity Score (DAS)-28, and so these may be potential biomarkers of disease progression and response. Conclusions: These data provide evidence that specific phosphoproteome and proteome signatures are associated with different RA pathotypes and may have clinical utility for stratifying patients as part of a personalised medicine approach.
HostingRepositoryPRIDE
AnnounceDate2024-08-08
AnnouncementXMLSubmission_2024-08-08_02:32:36.035.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD044963
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterVinothini Rajeeve
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-08-30 06:22:22ID requested
12024-08-08 02:32:36announced
Publication List
10.6019/PXD044963;
10.1186/s13075-024-03351-4;
Ç, ubuk C, Lau R, Cutillas P, Rajeeve V, John CR, Surace AEA, Hands R, Fossati-Jimack L, Lewis MJ, Pitzalis C, Phosphoproteomic profiling of early rheumatoid arthritis synovium reveals active signalling pathways and differentiates inflammatory pathotypes. Arthritis Res Ther, 26(1):120(2024) [pubmed]
Keyword List
submitter keyword: LC-MS/MS, mass spectrometry, label-free, phosphoproteomics
Contact List
Professor Pedro R Cutillas
contact affiliationMass Spectrometry Facility Barts Cancer Institute Queen Mary, University of London John Vane Science Centre, Charterhouse Square, London EC1M 6BQ
contact emailp.cutillas@qmul.ac.uk
lab head
Vinothini Rajeeve
contact affiliationCentre for Haemato Oncology
contact emailv.rajeeve@qmul.ac.uk
dataset submitter
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