RT Journal Article
T1 Lymphocyte Profile and Immune Checkpoint Expression in Drug-Induced Liver Injury: An Immunophenotyping Study
A1 Cueto-Sánchez, Alejandro
A1 Niu, Hao
A1 Del Campo-Herrera, Enrique
A1 Robles-Díaz, María Mercedes
A1 Sanabria-Cabrera, Judith Adriana
A1 Ortega-Alonso, Aida
A1 García-Cortés, Miren
A1 González-Grande, Rocío
A1 Jiménez-Pérez, Miguel
A1 Ruiz-Cabello, Francisco
A1 Andrade-Bellido, Raúl Jesús
A1 Lucena-González, María Isabel
K1 Hígado -- Enfermedades
K1 Inmunoterapia
AB The identification of specific HLA risk alleles in drug-induced liver injury (DILI) points toward an important role of the adaptive immune system in DILI development. In this study, we aimed to corroborate the role of an adaptive immune response in DILI through immunophenotyping of leukocyte populations and immune checkpoint expressions. Blood samples were collected from adjudicated DILI (n = 12), acute viral hepatitis (VH; n = 13), acute autoimmune hepatitis (AIH; n = 9), and acute liver injury of unknown etiology (n = 15) at day 1 (recognition), day 7, and day >30. Blood samples from patients with nonalcoholic fatty liver disease (NAFLD; n = 20) and healthy liver controls (HLCs; n = 54) were extracted at one time point. Leukocyte populations and immune checkpoint expressions were determined based on cell surface receptors, except for CTLA-4 that was determined intracellularly, using flow cytometry. At recognition, DILI demonstrated significantly higher levels of activated helper T-cell (P < 0.0001), activated cytotoxic T-cells (P = 0.0003), Th1 (P = 0.0358), intracellular CTLA-4 level in helper T-cells (P = 0.0192), and PD-L1 presenting monocytes (P = 0.0452) than HLC. These levels approached those of HLC over time. No significant differences were found between DILI and VH. However, DILI presented higher level of activated helper T-cells and CTLA-4 than NAFLD and lower PD-L1 level than AIH. Our findings suggest that an adaptive immune response is involved in DILI in which activated CD4+ and CD8+ play an important role. Increased expression of negative immune checkpoints is likely the effect of peripheral tolerance regulation.
PB Wiley
YR 2021
FD 2021-09-20
LK https://hdl.handle.net/10630/23504
UL https://hdl.handle.net/10630/23504
LA eng
NO Cueto-Sanchez A, Niu H, Del Campo-Herrera E, Robles-Díaz M, Sanabria-Cabrera J, Ortega-Alonso A, Garcia-Cortes M, Gonzalez-Grande R, Jimenez-Perez M, Ruiz-Cabello F, Andrade RJ, Lucena MI, Stephens C. Lymphocyte Profile and Immune Checkpoint Expression in Drug-Induced Liver Injury: An Immunophenotyping Study. Clin Pharmacol Ther. 2021 Dec;110(6):1604-1612. doi: 10.1002/cpt.2423.
NO The present study has been supported by grants of Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional – FEDER (contract numbers: PI19/00883, PI16/01748, P18-RT-3364-2020, and PT20/000127). CIBERehd and Plataforma ISCiii Ensayos Clínicos are funded by Instituto de Salud Carlos III. Funding for open access charge: Universidad de Málaga/CBUA. The funding sources had no involvement in the study design; in the collection, analysis, and interpretation of data; in the writing of the report, or in the decision to submit the manuscript for publication.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026