PXD044963

PXD044963 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteomic profiling discriminates between myeloid and lymphoid pathotypes in early RA synovium
Description	Background: 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.
HostingRepository	PRIDE
AnnounceDate	2024-08-08
AnnouncementXML	Submission_2024-08-08_02:32:36.035.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD044963
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Vinothini Rajeeve
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-30 06:22:22	ID requested
⏵ 1	2024-08-08 02:32:36	announced

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]

submitter keyword: LC-MS/MS, mass spectrometry, label-free, phosphoproteomics

Professor Pedro R Cutillas
contact affiliation	Mass Spectrometry Facility Barts Cancer Institute Queen Mary, University of London John Vane Science Centre, Charterhouse Square, London EC1M 6BQ
contact email	p.cutillas@qmul.ac.uk
lab head
Vinothini Rajeeve
contact affiliation	Centre for Haemato Oncology
contact email	v.rajeeve@qmul.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044963
     1. Label: PRIDE project
     2. Name: Phosphoproteomic profiling discriminates between myeloid and lymphoid pathotypes in early RA synovium