PXD070591

PXD070591 is an original dataset announced via ProteomeXchange.

Title	Asymmetrically glycosylated IgG1 antibodies are universal and drive human disease
Description	IgG antibodies have a conserved N-linked glycan on residue Asn297 of the homodimeric Fc region that modulates antibody-mediated effector functions. These effects on the immune response are reflected in correlations between IgG glycans and numerous infectious and autoimmune diseases. However, current studies fail to characterize these Asn297-linked glycans comprehensively, relying on glycan release methods. Here, we develop an intact LC/MS method to glycoprofile polyclonal IgG antibodies while preserving the Fc glycan spatial pairing. We analyze plasma samples from healthy and virally infected individuals and find that all individuals have asymmetrically glycosylated IgGs—the glycans on each of the Fc protomers are not identical. We find that the previously observed association between IgG afucosylation and severe dengue disease is due to asymmetric monofucosylation of IgGs, not symmetric afucosylation. Finally, we engineer monofucosylated IgG1s which are indistinguishable from afucosylated IgG1s in binding to FcγRIIIA in vitro and inducing effector functions in vivo.
HostingRepository	PRIDE
AnnounceDate	2025-11-18
AnnouncementXML	Submission_2025-11-18_03:13:08.041.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tala Azzam
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	complex glycosylation
Instrument	6545XT Q-TOF LC/MS

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-11 08:27:32	ID requested
⏵ 1	2025-11-18 03:13:08	announced

Dataset with its publication pending

submitter keyword: Antibody glycosylation

intact LC/MS

Eric J. Sundberg
contact affiliation	School of Medicine, Department of Biochemistry, Emory University
contact email	eric.sundberg@emory.edu
lab head
Tala Azzam
contact affiliation	Emory University
contact email	tala.azzam@emory.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD070591
     1. Label: PRIDE project
     2. Name: Asymmetrically glycosylated IgG1 antibodies are universal and drive human disease