PXD054336-1

PXD054336 is an original dataset announced via ProteomeXchange.

Title	Multitiered proteome analysis displays the hyperpermeability of the rheumatoid synovial compartment for plasma proteins
Description	Rheumatoid arthritis (RA) is characterized by synovial hyperplasia and cartilage/bone destruction. RA affects the synovial joints, the synovial lining and consequently the permeability of the synovium. As the latter is of central relevance for the distribution of systemically delivered therapeutics into synovial fluid (SF), we here assessed the protein composition of paired plasma and SF of patients diagnosed with RA at three distinct levels of depth using mass spectrometric approaches: the “total” proteome, the “total” IgG1 antibody repertoire and the RA-specific ACPA IgG1 autoantibody repertoire. The SF proteome was dominated by >150 plasma proteins, and we additionally detected several cartilage- and neutrophil-derived proteins of lower abundance. Strikingly, the plasma proteins were not only qualitatively reflected in SF but also quantitatively, independent of their size and/or other biochemical features. Also the synovial “total” IgG1 and autoreactive ACPA IgG1 repertoire highly resembled the IgG1 repertoires detected in plasma within the same patient. Our comprehensive multilayer data thus reveals that the proteome, including the dominant, most abundant (auto)antibody clones, present in SF of RA patients is a direct reflection of the proteome present in blood, spiked by the local (immune) processes within the RA joint. We thus conclude that proteins directly pass from blood into SF of these joints without substantial filtration bias. These findings thereby not only exemplify the use of in-depth multilayer proteome analyses to revisit basic concepts underlying RA pathology and to monitor the local (immune) processes destructive to cartilage, but also provide evidence indicating that (protein-based) therapeutics may equally enter SF of swollen joints and that pharmacokinetic analyses of such therapeutics in blood are directly relevant to the synovial compartment.
HostingRepository	PRIDE
AnnounceDate	2025-01-21
AnnouncementXML	Submission_2025-01-21_05:08:18.451.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sofia Kalaidopoulou Nteak
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-29 04:34:24	ID requested
⏵ 1	2025-01-21 05:08:19	announced

Stork EM, Kalaidopoulou Nteak S, van Rijswijck DMH, Damen JMA, Scherer HU, Toes REM, Bondt A, Huizinga TWJ, Heck AJR, Multitiered Proteome Analysis Displays the Hyperpermeability of the Rheumatoid Synovial Compartment for Plasma Proteins. Mol Cell Proteomics, 24(2):100900(2024) [pubmed]

10.1016/j.mcpro.2024.100900;

submitter keyword: paired plasma and synovial fluid proteomics

repertoire profiling

IgG1

ACPA

Albert J.
contact affiliation	Biomolecular Mass Spectrometry and Proteomics,Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, Utrecht 3584 CH, The Netherlands Netherlands Proteomics Center, Padualaan 8, Utrecht 3584 CH, the Netherlands
contact email	A.J.R.Heck@uu.nl
lab head
Sofia Kalaidopoulou Nteak
contact affiliation	Biomolecular Mass Spectrometry and Proteomics Utrecht University
contact email	s.kalaidopoulounteak@uu.nl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/01/PXD054336

PRIDE project URI

• PRIDE
  1. PXD054336
     1. Label: PRIDE project
     2. Name: Multitiered proteome analysis displays the hyperpermeability of the rheumatoid synovial compartment for plasma proteins