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Inicio Annals of Hepatology O-2 ROLE OF IMMUNE CHECKPOINTS AND ACTIVATED HELPER AND CYTOTOXIC T-CELLS IN DRU...
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Vol. 24. Issue S1.
Abstracts of the 2021 Annual meeting of the ALEH (Asociación Latinoamericana para el Estudio del Hígado)
(September 2021)
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Vol. 24. Issue S1.
Abstracts of the 2021 Annual meeting of the ALEH (Asociación Latinoamericana para el Estudio del Hígado)
(September 2021)
Open Access
O-2 ROLE OF IMMUNE CHECKPOINTS AND ACTIVATED HELPER AND CYTOTOXIC T-CELLS IN DRUG-INDUCED LIVER INJURY (DILI)
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Alejandro Cueto-Sanchez1, Judith Sanabria Cabrera1,2, Mercedes Robles-Diaz1,3, Aida Ortega-Alonso1, Miren Garcia Cortes1,3, Enrique del Campo-Herrera1, Rocio Gonzalez-Grande4, Miguel Jimenez-Perez4, Francisco Ruiz-Cabello5, M Isabel Lucena1,2,3, Camilla Stephens1,3, Raúl J Andrade1,3
1 Servicio de Farmacología Clínica and UGC Aparato Digestivo, Instituto de Investigación Biomédica de Málaga-Ibima, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain
2 Platform ISCIII for Clinical Research Clinical Trials UICEC-Ibima, Málaga, Spain
3 Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
4 Servicio de Aparato Digestivo, IBIMA, Hospital Universitario Regional de Málaga, Málaga, Spain
5 Servicio de Análisis Clínicos e Inmunología, UGC de Laboratorio Clínico, Hospital Universitario Virgen de las Nieves, Granada, Spain
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Vol. 24. Issue S1

Abstracts of the 2021 Annual meeting of the ALEH (Asociación Latinoamericana para el Estudio del Hígado)

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Introduction

Idiosyncratic DILI is a challenging condition, believed to involve the immune system. This hypothesis is supported by various identified HLA risk alleles.

Objectives

To evaluate a potential role of the immune system in DILI through leukocyte immunophenotyping.

Methods

Blood samples were collected from adjudicated DILI (n=12) and viral hepatitis (VH, 13) at day 1 (recognition), 7 and >30. A single blood sample was extracted from healthy liver controls (HLC, 54). Leukocyte populations and immune checkpoint expressions were determined based on cell surface receptors, except for CTLA-4 that was determined intracellularly, using multiparametric flow cytometry.

Results

No differences were detected in leukocytes, lymphocytes or neutrophils counts at day 1. However, DILI (0.57 × 10E09/L, p=0.037) and HV (1.41 × 10E09/L, p<0.0001) had increased monocyte levels than HLC (0.35 × 10E09/L). At day 1 DILI presented higher levels of activated helper T-cells (CD4+/DR+) and activated cytotoxic T-cells (CD8+/DR+) than HLC (14%vs6.3%, p<0.0001; 31%vs15%, p=0.0003, respectively). The same trend was detected for VH. A strong correlation between activated CD4+ and CD8+ was found in DILI (r=0.85, p<0.001), but less in VH (r=0.58, p=0.0015). Regarding helper T-cell subpopulations, DILI had higher level of Th1 (52vs42%, p=0.0358), while VH had lower level of Th9 than HLC (13%vs18%, p=0.0112). Regarding immune checkpoint expressions on CD4+, DILI presented higher intracellular CTLA-4 level than HLC (28%vs18%, p=0.0192). Higher expression of checkpoint ligand PD-1L on monocytes was also found in DILI (5.3%vs3.4%, p=0.0452) and VH (9.1%vs3.4%, p<0.0001). The level of all leukocyte populations and checkpoint expressions in DILI and VH approached HLC levels in the later samples, except for CD28 and CD86 that are constitutively expressed.

Conclusion

Our findings suggest that an adaptive immune response is involved in DILI in which activated CD4+ and CD8+ play important roles. Increased expression of negative immune checkpoints and ligands reflects restoration of immune homeostasis. Funding:PI16/01748, PI19/00883, CIBERehd-ISCIII

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