PXD021441

PXD021441 is an original dataset announced via ProteomeXchange.

Title	Proteomic analyses of plasma-derived exosomes in IgG4-RD and its potential role in B cell differentiation and tissue damage
Description	Objective: This study aimed to investigate plasma exosome profiling of IgG4-RD and its potential role in B cell differentiation and tissue damage. Methods: One hundred untreated IgG4-RD patients and 135 sex, age matched healthy controls (HCs) were enrolled in this study. A combination of liquid chromatography-tandem mass spectroscopy (LC-MS/MS) and TMT label quantitation was used to detect exosome and B cell profiling. To validate differentially expressed proteins, western blot and ELISA were performed. RT-qPCR was used to detect gene expression after exosome stimulation. Flowcytometry was used to measure B cell activation, apoptosis, differentiation and reactive oxygen species (ROS) expression. Besides, correlation analysis between differentially expressed complement protein and laboratory parameters was also performed. Results: In total, 82 proteins were upregulated and 96 proteins were downregulated in exosome of IgG4-RD patients compared with HCs. Pathway analysis revealed that complement cascade pathway in exosome of IgG4-RD was activated, together with reduced C3 complement and C5 complement. Validation by ELISA and WB, exosome C3 and C5 was decrease in IgG4-RD compared with HCs. Stimulation of B cells with exosome, naïve B cells decreased, while memory B cells and plasmablast were increased together with increased CYCS with activation of downstream complement system. ROS was increased in B cells of IgG4-RD compared with HC. In affected submandibular glands, BCR signaling pathway was activated and exosome may potentially participate in tissue damage. Conclusion: There were 82 differentially expressed upregulated proteins and 96 downregulated proteins in IgG4-RD exosome compared with HCs. Differentially expressed proteins were enriched in exosome, complement function and immune response indicating complement activation in exosome may be related to IgG4-RD. Reduced C3 and C5 expression in exosome of IgG4-RD may indicate the disease severity. Our research suggests that IgG4-RD exosomes can participate in the differentiation B cells into plasmablast, activate the B cell auto-oxidative damage pathway and potentially participate in the pathogenesis of IgG4-RD.
HostingRepository	iProX
AnnounceDate	2020-09-14
AnnouncementXML	Submission_2023-08-24_21:12:35.068.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shengyu Zhang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-13 19:49:30	ID requested
1	2020-09-13 19:51:23	announced
⏵ 2	2023-08-24 21:12:35	announced	2023-08-25: Update publication information.

Zhang P, Zhang Y, Pan M, Liu Z, Li J, Peng L, Zhou J, Hu C, Liu S, Zeng X, Ge W, Zhang W, Proteomic analyses of plasma-derived exosomes in immunoglobulin (Ig) G4-related disease and their potential roles in B cell differentiation and tissue damage. J Autoimmun, 122():102650(2021) [pubmed]

submitter keyword: Proteomic, IgG4-RD, exosomes, B cell

Wei Ge
contact affiliation	Institute of Basic Medical Sciences Chinese Academy of Medical Sciences
contact email	wei.ge@chem.ox.ac.uk
lab head
Shengyu Zhang
contact affiliation	Institute of Basic Medical Sciences Chinese Academy of Medical Sciences
contact email	zhendezy@163.com
dataset submitter

iProX dataset URI