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PXD035854

PXD035854 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMinor Antigens in Membranous Nephropathy Identified by Mass Spectrometry
DescriptionBackground: Multiple autoantigens have been identified in membranous nephropathy (MN) by tissue-based proteomics. However, the antigenic targets of disease are unknown for >10% of MN and >50% of membranous lupus nephritis (MLN) cases. We identified multiple new targets in PLA2R-/THSD7A-/EXT-/NELL1-quadruple negative MN biopsies through mass spectrometry (MS) of immune complexes recovered from biopsy tissue of patients with MN. Methods: MN cases negative for PLA2R, THSD7A, EXT1/2, and NELL1 were identified from a biopsy database. Protein G immunoprecipitation was used to recover immune complexes from frozen biopsy tissue, followed by interrogation by mass spectrometry (MS). Potential antigens were confirmed through paraffin immunofluorescence of protein targets, followed by co-localization with IgG within immune deposits. Consecutive series of 165 cases of PLA2R-negative MN biopsies and 95 MLN biopsies was screened to determine the frequency for each potential antigen. Results: Seven protein targets were discovered within immune complexes from MN biopsies including FCN3, CD206, EEA1, SEZ6L2, NPR3, MST1, and VASN. Peptides from these proteins on MS were not enriched in PLA2R (n=86), THSD7A (n=64), NELL1 (n=64), or EXT1/2 (n=60) controls. Between 3-30 unique peptides were detected for each target. Frequencies of each antigen, determined by staining consecutive case series, were SEZ6L2 (1/165 idiopathic; 0/95 MLN), VASN (8/165 idiopathic; 2/95 MLN), EEA1 (6/165 idiopathic; 7/95 MLN), MST1 (6/165 idiopathic; 2/95 MLN), and FCN3 (0/165 idiopathic, 6/95 MLN), NPR3 and CD206 were positive in index cases. All cases showed co-localization of IgG within immune deposits. Conclusion: Seven novel protein targets were identified in MN and MLN.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:44:37.469.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAaron Storey
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-08-07 03:42:54ID requested
12023-04-06 13:03:19announced
22023-11-14 08:44:38announced2023-11-14: Updated project metadata.
Publication List
Caza TN, Storey AJ, Hassen SI, Herzog C, Edmondson RD, Arthur JM, Kenan DJ, Larsen CP, Discovery of seven novel putative antigens in membranous nephropathy and membranous lupus nephritis identified by mass spectrometry. Kidney Int, 103(3):593-606(2023) [pubmed]
Keyword List
submitter keyword: Human, Kidney, Pulldown, Membranous Nephropathy, DDA
Contact List
Chris Larsen
contact affiliation1Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock, AR 72211
contact emailchris.larsen@arkanalabs.com
lab head
Aaron Storey
contact affiliationUniversity of Arkansas for Medical Sciences
contact emailajstorey@uams.edu
dataset submitter
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