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单细胞测序揭示肾移植受者抗体介导排斥反应的潜在机制

郑凯乐 付嘉钊 尤佳 吴丹 王学彬 王卓

中国临床药理学与治疗学2026,Vol.31Issue(3):289-299,11.
中国临床药理学与治疗学2026,Vol.31Issue(3):289-299,11.DOI:10.12092/j.issn.1009-2501.2026.03.001

单细胞测序揭示肾移植受者抗体介导排斥反应的潜在机制

Single-cell sequencing reveals the underlying mechanism of antibody-mediated rejection in renal transplant recipients

郑凯乐 1付嘉钊 2尤佳 1吴丹 3王学彬 4王卓5

作者信息

  • 1. 蚌埠医科大学药学院,蚌埠 233030,安徽||上海市儿童医院药学部,上海 200062||海军军医大学第一附属医院药剂科,上海 200433
  • 2. 海军军医大学第一附属医院器官移植科,上海 200433
  • 3. 上海市儿童医院生物信息学中心,上海 200062
  • 4. 上海市儿童医院药学部,上海 200062||海军军医大学第一附属医院药剂科,上海 200433
  • 5. 海军军医大学第一附属医院药剂科,上海 200433
  • 折叠

摘要

Abstract

AIM:Based on single-cell sequencing analysis,the underlying mechanism of antibody-mediated rejection(ABMR)in kidney transplant re-cipients.METHODS:Recipients with 6 months or more after kidney transplantation were selected as research subjects,and high-resolution scRNA-seq analysis of immune cell subsets in peripheral blood mononuclear cells(PBMC)was performed using sin-gle-cell RNA sequencing(scRNA-seq)technology.Flow cytometry was used to examine the effect of differential genes on renal transplant ABMR in dif-ferent immune cell populations.RESULTS:This study analyzed differential gene expression be-tween ABMR patients and healthy controls using single-cell sequencing technology,identifying CD69,CD83,CD52,CD74,and CX3CR1 as key differentially expressed genes.In classical monocytes,ABMR pa-tients exhibited increased CD83 and CD52 gene ex-pression levels compared to the control group,which showed a downward trend after treatment.Regarding initial CD4+T cells,ABMR patients demon-strated significantly reduced CD69 gene expression.In NK cells,ABMR patients displayed decreased CX3CR1 gene expression initially,with further re-duction in its geometric mean value post-treat-ment.Conversely,the geometric mean value of CD74 showed an increasing trend.CONCLUSION:In classical mononuclear cells,upregulated expression of CD83 and CD52 genes correlates with enhanced antigen-presenting cell functionality,thereby pro-moting the development of antigen-bonded mi-croenvironment remodeling(ABMR).In initial CD4+T cells,elevated CD69 gene expression is associated with T cell activation and proliferation,further con-tributing to ABMR progression.Conversely,down-regulated CX3CR1 gene expression in NK cells re-lates to impaired immune surveillance mechanisms,which partially inhibits ABMR formation.

关键词

他克莫司/肾移植/排斥反应/差异基因/PBMC

Key words

tacrolimus/kidney transplantation/rejection/differential gene/PBMC

分类

医药卫生

引用本文复制引用

郑凯乐,付嘉钊,尤佳,吴丹,王学彬,王卓..单细胞测序揭示肾移植受者抗体介导排斥反应的潜在机制[J].中国临床药理学与治疗学,2026,31(3):289-299,11.

基金项目

国家自然科学基金资助项目(82173900) (82173900)

促进市级医院临床技能与临床创新能力三年行动计划(SHDC2020CR4072) (SHDC2020CR4072)

2022年上海青年药学人才能力提升项目(沪药会字[2023]04号) (沪药会字[2023]04号)

上海市儿童医院人才引进启动项目(SHSERTYY20250505) (SHSERTYY20250505)

中国临床药理学与治疗学

1009-2501

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