PXD075232

PXD075232 is an original dataset announced via ProteomeXchange.

Title	Utility of monocyte-derived cells to investigate immune-mediated drug-induced liver injury
Description	Background & Aims: Immune-mediated drug-induced liver injury (DILI) is triggered or exacerbated by the immune system mounting an attack against the drug or its metabolites. The array of in vitro assays for evaluating intrinsic immunogenicity of drugs is limited, highlighting a significant gap in effectively predicting and understanding immune-mediated hepatotoxicity. We aimed to investigate whether monocytes differentiated with the metaheps protocol (MH) could provide insights into the molecular mechanisms of immune-mediated DILI. Methods: MH were generated from monocytes of healthy volunteers (HV) and DILI patients. MH phenotypic characterization was performed by proteomics and qPCR. MH sensitivity to immunogenic drugs was assessed by lactate dehydrogenase (LDH) assay. Drug-induced LDH release by DILI-derived MH was compared to the upper limit of the 95% CI calculated from HV-derived MH cells treated with the same drug. The 95% CI determined in HV-derived MH was set as sensitivity threshold for the specific drug. Results: MH cells retain the expression of several immune-related proteins of the parental monocytes and activate a pro-inflammatory response upon exposure to lipopolysaccharide. For most MH (5 out of 6) generated from patients with penicillin-induced DILI, the LDH release upon re-challenge was above the threshold. The sensitivity of MH generated from seven patients with immune checkpoint inhibitor (ICI)-induced hepatotoxicity was ICI-dependent, responding to nivolumab and/or ipilimumab (4 out of 5), but not to pembrolizumab (0 out of 2). Additionally, DILI-derived MH were not sensitive to non-DILI drugs. Conclusions: Monocyte-derived cells may serve as an additional tool for drug-specific mechanistic studies of immune-mediated DILI.
HostingRepository	PRIDE
AnnounceDate	2026-08-21
AnnouncementXML	Submission_2026-08-21_03:44:17.000.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michele Visentin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-04 14:22:06	ID requested
⏵ 1	2026-08-21 03:44:17	announced

10.1016/j.toxlet.2026.113176;

Ulepic M, Vargas MF, Astbury S, Rausch M, Pfammatter S, Samodelov SL, Grove JI, Kullak-Ublick GA, Hannan NRF, Aithal GP, Visentin M, Utility of monocyte-derived cells to investigate immune-mediated drug-induced liver injury. Toxicol Lett, 424():113176(2026) [pubmed]

submitter keyword: DILI, Monocytes, Drug-induced liver injury,Amoxicillin-Clavulanate, Immune Checkpoint Inhibitors, MetaHeps

Michele Visentin
contact affiliation	Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, 8006 Zurich, Switzerland
contact email	michele.visentin@usz.ch
lab head
Michele Visentin
contact affiliation	University Zurich
contact email	michele.visentin@usz.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD075232
     1. Label: PRIDE project
     2. Name: Utility of monocyte-derived cells to investigate immune-mediated drug-induced liver injury