PXD076368

PXD076368 is an original dataset announced via ProteomeXchange.

Title	Secreted tryptophanyl-tRNA synthetase levels predict severe systemic and neurological toxicities following CAR T therapy
Description	CAR T therapy is constrained by life-threatening cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), interrelated toxicities with poorly defined upstream triggers. While both toxicities involve aberrant myeloid activation, their shared initial drivers remain elusive. Through proteomic profiling of patient samples, we identified secreted tryptophanyl-tRNA synthetase (WRS) as a key signature of these adverse events. Cohort analyses reveal plasma WRS as a unifying predictive biomarker for both toxicities. Mechanistically, aggregated WRS, not the diffused form, is pathogenic under the low-sodium microenvironment. Aggregated WRS was detected in both the plasma and central nervous system under pathological conditions, and functionally validated as a potential driver of both toxicities. Therapeutically targeting the WRS circuit in humanized mouse models attenuates both systemic and neurological toxicities. Our bedside-to-bench investigative pipeline establishes WRS as a molecular nexus linking CRS and neurotoxicity, offering an integrated strategy to improve CAR T treatment safety.
HostingRepository	PRIDE
AnnounceDate	2026-09-05
AnnouncementXML	Submission_2026-09-04_18:29:43.229.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jiaqi Li
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-31 04:18:40	ID requested
⏵ 1	2026-09-04 18:29:43	announced

Dataset with its publication pending

submitter keyword: Cytokine release syndrome

CAR T therapy

Xiaoyu Hu
contact affiliation	Institute for Immunology, Tsinghua University; Beijing, China
contact email	huxiaoyu@westlake.edu.cn
lab head
Jiaqi Li
contact affiliation	Tsinghua university
contact email	ljq20@mails.tsinghua.edu.cn
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/2026/09/PXD076368

PRIDE project URI

• PRIDE
  1. PXD076368
     1. Label: PRIDE project
     2. Name: Secreted tryptophanyl-tRNA synthetase levels predict severe systemic and neurological toxicities following CAR T therapy