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PXD002475

PXD002475 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleHCV Cryoprecipitate LC-MS/MS with iTRAQ Quantification
DescriptionThe discovery of hepatitis C virus (HCV) in 1989 revealed the virus as the etiology of 40%-90% of the “essential” mixed cryoglobulinemia, where immune complex forms deposit called cryoprecipitate at temperatures below 37 °C. Cryoprecipitate constitutes monoclonal IgM and polyclonal IgG, some of which has reactivity against HCV core and NS3 epitopes. Resultant immune complex is considered entrapped on microvascular endothelium via C1q receptor, leading to complement activation and organ injury presenting predominantly as dermopathy, peripheral neuropathy and nephropathy. However, currently little is known on whether auto-reactive, cold-precipitating IgG components enriched in cryoprecipitate may play some role on the deposition of immune complex and subsequent complement-mediated injury of specific organs. Recently, with the advent of high-throughput immune repertoire sequencing and mass spectrometry, technical feasibility is growing to delineate antibodies of interest and their sequences directly from serum. To date, vast majority of studies actually utilized the antigen column for affinity purification of antibodies of interest, although this strategy is not applicable to disease entity with unknown antigen involvement. In such cases, disease-specific and organ-specific immune deposits may be a good alternative source of etiological antibodies. Herein, targeting HCV cryoglobulinemic vasculitis as a model, we conducted a proof-of-concept study aiming at characterizing the IgG components most prone to cryoprecipitation. To this end, we longitudinally studied one patient with cryoglobulinemic vasculitis with chronic HCV infection. After obtaining informed consent, cryoprecipitate and supernatant were separated from peripheral blood sample. Fab fragments from Protein G-purified IgG were recovered after papain digestion for isobaric tags for relative and absolute quantification (iTRAQ)-based quantitative proteomics. Simultaneously, total RNA was isolated from peripheral blood, and immunoglobulin heavy chain variable region (IGHV) was PCR-amplified with unique molecular identifier (UMI) strategy to construct a personal IGHV sequence library of immunoglobulin variable region. Sequencing output from MiSeq was bioinformatically converted into mass spectrometry database. Search was performed using MaxQuant software.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:05:29.735.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMasato Ogishi
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiTRAQ4plex-116 reporter+balance reagent acylated residue
InstrumentLTQ Orbitrap Elite
Dataset History
RevisionDatetimeStatusChangeLog Entry
02015-07-06 01:10:52ID requested
12016-07-14 00:08:34announced
22024-10-22 04:05:38announced2024-10-22: Updated project metadata.
Publication List
Ogishi M, Yotsuyanagi H, Moriya K, Koike K, Delineation of autoantibody repertoire through differential proteogenomics in hepatitis C virus-induced cryoglobulinemia. Sci Rep, 6():29532(2016) [pubmed]
10.1038/srep29532;
Keyword List
curator keyword: Biomedical
submitter keyword: Human, HCV, Immunoglobulin, Antibody, iTRAQ
Contact List
Hiroshi Yotsuyanagi
contact affiliationDepartment of Infectious Diseases Internal Medicine Graduate School of Medicine University of Tokyo, Japan
contact emailhyotsu-tky@umin.ac.jp
lab head
Masato Ogishi
contact affiliationThe University of Tokyo
contact emailoogishi-tky@umin.ac.jp
dataset submitter
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Dataset FTP location
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PRIDE project URI
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