RT Journal Article
T1 Immunophenotyping to improve the mechanistic understanding of idiosyncratic drug-induced liver injury: clinical implications and future directions
A1 Cueto Sánchez, Alejandro José
A1 Di Zeo-Sánchez, Daniel Enrique
A1 Segovia-Zafra, Antonio
A1 Matilla-Cabello, Gonzalo
A1 Bodoque-García, Ana
A1 Lucena-González, María Isabel
A1 Villanueva-Paz, Marina
K1 Hepatotoxicidad
K1 Hígado - Efectos de los medicamentos
K1 Hígado - Enfermedades
K1 Inmunodiagnóstico
K1 Diagnóstico de laboratorio
AB The late event onset of a fraction of idiosyncratic drug-induced liver injury (DILI) cases and the link observed by genome-wide association studies (GWASs) of certain human leucocyte antigen (HLA) alleles with DILI due to specific drugs support the crucial role of the immune system (both innate and adaptive) in the pathogenesis of DILI. Recent advances in both flow and mass cytometry have allowed the profiling of all major immune cell types in a given sample. Therefore, determining the lymphocyte populations in samples from patients with DILI would facilitate the development of specific biomarkers for DILI diagnosis and prognosis. To date, a few studies have explored the immune landscape in DILI. In a recent study of leukocyte immunophenotyping using flow cytometry from the Spanish DILI Registry, an important role of adaptive immune response in DILI is suggested. DILI patients had significantly higher levels of T helper 1 (Th1) cells and activated helper and cytotoxic T cells than healthy controls. Furthermore, the increased expression of negative immune checkpoints and ligands in DILI patients could reflect a restoration of the immune homeostasis. Differences in the profile of cytokines in DILI patients from the Drug-Induced Liver Injury Network (DILIN) also suggest an involvement of both innate and adaptive immune systems in DILI development and prognosis. Moreover, several studies based on immunophenotyping of liver infiltrates showed a distinctive pattern of cellular infiltrates in patients with immune checkpoint inhibitors (ICIs)-DILI, with lower levels of plasma cells, CD20+ B cells and CD4+ T cells than in autoimmune hepatitis (AIH) patients. These pioneering studies highlight the importance of immunophenotyping for the mechanistic understanding of DILI. In this review, available data on immunophenotyping in DILI are gathered, and the potential clinical applications of cutting-edge, novel immunophenotyping techniques are discussed.
PB Open Exploration
YR 2023
FD 2023-04-26
LK https://hdl.handle.net/10630/38177
UL https://hdl.handle.net/10630/38177
LA eng
NO Cueto-Sánchez A, Di Zeo-Sánchez DE, Segovia-Zafra A, Matilla-Cabello G, Bodoque-Garcí�a A, Lucena MI, et al. Immunophenotyping to improve the mechanistic understanding of idiosyncratic drug-induced liver injury: clinical implications and future directions. Explor Dig Dis. 2023;2:56–76. https://doi.org/10.37349/edd.2023.00018
NO This work was supported by grants from the Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional (FEDER), contract numbers: [PI21/01248], [PI19-00883], [PT 20/00127], [UMA18-FEDERJA-194], [PY18-3364]; and grants from Consejería de Salud de Andalucía cofounded by FEDER, contract number: [PEMP-0127-2020]. Marina Villanueva-Paz holds a Sara Borrell [CD21/00198] research contract from Instituto de Salud Carlos III (ISCIII) and Consejería de Salud de Andalucía.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026