Monocytic Expression of HLA-DR After Liver Transplantation

Summary

A defect of the immune response has been described in patients with severe liver disease. This immune-paresis is partly driven by a compensatory anti-inflammatory response following a systemic inflammatory response syndrome and affects the innate immune response. The innate immune defect has been described in patients with advanced cirrhosis and more significantly in patients with acute liver failure or acute on chronic liver failure (ACLF). The monocytes/macrophages pro-inflammatory response and finally the antimicrobial response are thus strongly impaired, leading to higher sepsis risk. The monocytes/macrophages phenotype associated with these functional alterations has been widely described, with a weaker expression of Human Leukocyte Antigen - DR isotype (HLA-DR) on the monocytes surface, correlated with poor outcomes. The low monocytic expression of HLA-DR, its functional and clinical impact has been widely described in the context of septic shock with similar pathophysiological mechanisms.

Liver transplantation (LT) is often the only therapeutic option for patients with advanced liver failure. Post-transplant survival of the most severe patients is similar to the survival in the whole population of LT patients, but the complication rate remains higher, with a major risk of infection. Currently used immunosuppression protocols do not take into account the quality of pre-transplant immune response. Some treatments, such as corticosteroids, which are widely used for the induction of post-transplant immunosuppression, may affect the innate immune response. However, it has been shown that low expression of post-transplant monocyte HLA-DR was associated with a greater risk of septic complication.

The general objective of this study is to focus on the evolution of a robust marker of immune dysfunction, HLA-DR monocyte expression, before and following LT, and to analyse its post LT expression depending on the level of pre-transplant expression as well as its association with post-transplant complications. This study will bring new insights for the design of a prospective study on the relevance of adapting post-transplant immunosuppression protocols to HLA-DR expression on monocytes surface, which is a robust marker of the innate immune response.

Evaluation of innate immune dysfunction pre-LT by quantification of monocytic HLA-DR expression and monitoring of its post-LT kinetics may be relevant for assessing post-transplant immune status and adapting immunosuppressive therapy. A descriptive, observational study associating clinical and biological data is needed to confirm the relevance of HLA-DR expression quantification on the surface of monocytes in a population of selected patients, before and after LT. These data will allow setting up a prospective interventional study reporting the possible benefit of post-transplant immunosuppressive treatment modulation, according to the HLA-DR monocyte dosage and its kinetics evolution.

The main objective of this study is to describe the association between evolution of monocytic HLA-DR expression on monocytes/macrophages surface during the first month after LT and the occurrence of one of the 2 following clinical events reflecting a post LT immune dysfunction (acute cell rejection and sepsis).

Conditions

• Liver Diseases
• Liver Transplantation
• Cirrhosis, Liver

Interventions

BIOLOGICAL

blood sample

Samples will be collected at the inclusion and repeated if necessary before LT, including one 4 mL EDTA sample and one 4 mL Heparin sample and one 2.5 mL PAXgene® sample, allowing the HLA-DR assay to be performed with also plasma aliquots and messenger RNAs. Same samples will also be collected : * between inclusion and LT in case of major clinical change * During the pre-transplant follow-up 3 months after inclusion, for patients who have not been transplanted within 3 months after inclusion * at day 1 after LT * 2 times a week after the LT for a maximum of 1 month Biological data will be collected at those different times.

Sponsors & Collaborators

• Hospices Civils de Lyon

  lead OTHER

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-02-26

Primary Completion

2023-07-14

Completion

2023-07-14

Countries

• France

Study Locations