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Published on: September 7, 2022
Single-cell analysis unveils immune dysregulation and EBV-driven lymphoproliferative disorder in pediatric liver
Yanling Wen1, Chen Chen2, Tao Zhou2
1Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, China.
Insights
Post-transplant lymphoproliferative disorder (PTLD) in pediatric liver transplant patients involves significant immune dysregulation. Epstein-Barr virus (EBV) infection exacerbates this, impairing T cell and B cell functions, leading to PTLD development.
Area of Science:
- Immunology
- Transplantation Medicine
- Virology
Background:
- Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after liver transplantation, especially in children.
- Epstein-Barr virus (EBV) infection is strongly linked to PTLD incidence, but the underlying immune microenvironment changes are not fully understood.
Purpose of the Study:
- To investigate the immune cell landscape and molecular alterations in pediatric liver transplant recipients with and without PTLD, focusing on the role of EBV infection.
- To elucidate the impact of EBV on specific immune cell populations within the PTLD microenvironment.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) was employed to analyze peripheral blood mononuclear cells (PBMCs).
- Four groups were studied: PTLD patients with EBV, EBV-positive non-PTLD recipients, EBV-negative recipients, and healthy children.
Main Results:
- PTLD patients displayed significant immune dysregulation, including reduced NK cell cytotoxicity, impaired B cell differentiation, and altered myeloid cell inflammatory profiles.
- EBV infection in PTLD primarily affected memory B cells and plasma cells, compromising their function even in uninfected cells.
- CD8+ T cells showed increased exhaustion and reduced cytotoxic activity, while regulatory T cells exhibited enhanced suppressive functions in PTLD patients.
Conclusions:
- This study provides a detailed map of the immune microenvironment in pediatric PTLD, highlighting key cellular changes driven by EBV infection.
- Findings identify critical immune alterations associated with PTLD development and suggest potential therapeutic targets for restoring immune balance and controlling EBV-driven lymphoproliferation.
Abstract:
Post-transplant lymphoproliferative disorder (PTLD) is a severe complication following liver transplantation, particularly in pediatric patients, with a high incidence rate associated with Epstein-Barr virus (EBV) infection. The immunological microenvironment of PTLD, particularly the cellular and molecular changes associated with EBV infection, remains unclear. Using scRNA-seq, we examined changes in the immune microenvironment of PBMC from pediatric liver transplant recipients across four groups: PTLD patients with EBV infection, EBV-positive non-PTLD transplant recipients, EBV-negative transplant recipients, and healthy children. PTLD patients exhibited profound immune dysregulation, marked by weakened cytotoxicity in NK cells, reduced B cell differentiation and activation, and an inflammatory shift in myeloid cells. EBV infection primarily targeted memory B cells and plasma cells in PTLD patients, with uninfected memory B cells showing impaired functional potential. Furthermore, CD8+ T cells in PTLD were characterized by increased exhaustion and low cytotoxic activity. In addition, regulatory T cells in PTLD displayed enhanced suppressive functions. Our findings present an in-depth view of the immune landscape in PTLD, identifying key immune cell alterations associated with EBV infection and PTLD development. These insights could inform the development of targeted therapies aimed at restoring immune function and controlling EBV-driven lymphoproliferation in pediatric liver transplant recipients.
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