关键词: 移植后淋巴增生性疾病 ,  , EB 病毒 , 单细胞测序 , 儿童肝移植

Abstract:

Objective Post-transplant lymphoproliferative disorder （PTLD） is a severe complication following liver transplantation， particularly in pediatric patients， with a high incidence rate associated with EpsteinBarr virus （EBV） infection. The immunological microenvironment of PTLD， particularly the cellular and molecular changes associated with EBV infection， remains unclear. Methods Using single-cell RNA sequencing（scRNAseq）， we examined changes in the immune microenvironment of peripheral blood mononuclear cell（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. Results 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 PTLDwere characterized by increased exhaustion and low cytotoxic activity. In addition， regulatory T cells in PTLD displayed enhanced suppressive functions. Conclusion 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 informthe development of targeted therapies aimed at restoring immune function and controlling EBV-driven lymphoproliferation in pediatric liver transplant recipients.

Key words: Post-transplant lymphoproliferative disease ,  , Epstein-Barr virus ,  , Single-cell RNA-sequencing