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Biomarkers of pediatric Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis through single-cell transcriptomics

Author

Listed:
  • Jie Shen

    (Central South University
    Hunan Clinical Research Center of Pediatric Cancer
    Furong Laboratory)

  • Yunyan He

    (The First Affiliated Hospital of Guangxi Medical University)

  • Hong Zheng

    (Central South University
    Hunan Clinical Research Center of Pediatric Cancer
    Furong Laboratory
    Central South University)

  • Jianwen Xiao

    (Children Hospital of Chongqing Medical University)

  • Fu Li

    (Children’s Hospital Affiliated to Shandong University and Jinan Children’s Hospital)

  • Keke Chen

    (Children’s Medical Center of Hunan Provincial People’s Hospital of the First-Affiliated Hospital)

  • Biyun Guo

    (The First Affiliated Hospital of Xiamen University)

  • Yulei He

    (University of Electronic Science and Technology of China)

  • Lin Liu

    (Central South University
    Hunan Clinical Research Center of Pediatric Cancer
    Furong Laboratory)

  • Zhi Lin

    (Central South University
    Hunan Clinical Research Center of Pediatric Cancer
    Furong Laboratory)

  • Dan Wang

    (Central South University
    Hunan Clinical Research Center of Pediatric Cancer
    Furong Laboratory)

  • Leping Liu

    (Central South University
    Hunan Clinical Research Center of Pediatric Cancer
    Furong Laboratory)

  • Shengfeng Wang

    (Central South University
    Hunan Clinical Research Center of Pediatric Cancer
    Furong Laboratory
    Central South University)

  • Wen Zhou

    (Central South University)

  • Yingchi Zhang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Jian Wei

    (Xiangxi Autonomous Prefecture People’s Hospital)

  • Yunchu Wang

    (Liuyang people’s hospital)

  • Rong Hu

    (The First People’s Hospital of Changde City)

  • Daolin Tang

    (UT Southwestern Medical Center)

  • Dao Wang

    (The First Affiliated Hospital of Zhengzhou University)

  • Minghua Yang

    (Central South University
    Hunan Clinical Research Center of Pediatric Cancer
    Furong Laboratory)

Abstract

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a fatal hyperinflammatory disorder distinct from self-limiting EBV-induced infectious mononucleosis (IM). However, the immunological mechanisms underlying the divergence between benign EBV infection and fulminant HLH—particularly in the absence of inherited immunodeficiency—remains unclear, and systematic comparisons of immune landscapes across EBV-associated disease spectra are lacking. In this study, by enrolling children with IM and healthy volunteers as controls, we utilize single-cell RNA sequencing to identify unique immunological characteristics of EBV-HLH. Our analysis indicates that patients with EBV-HLH exhibite widespread activation of NF-κB signaling pathway. Furthermore, excessive cytokine secretion by T and NK cells is observed, along with a shift in monocyte differentiation towards an inflammatory phenotype, and the aggregation of IDO1+ monocytes. Metabolic pathway analysis reveals that L-kynurenine, a downstream metabolite of IDO1, is specifically elevated in EBV-HLH and mediates the production of multiple pro-inflammatory cytokines. Collectively, our study maps the immune landscape in pediatric EBV-HLH at single-cell resolution, uncovering potential role of IDO1+ monocytes and L-kynurenine as biomarkers.

Suggested Citation

  • Jie Shen & Yunyan He & Hong Zheng & Jianwen Xiao & Fu Li & Keke Chen & Biyun Guo & Yulei He & Lin Liu & Zhi Lin & Dan Wang & Leping Liu & Shengfeng Wang & Wen Zhou & Yingchi Zhang & Jian Wei & Yunchu , 2025. "Biomarkers of pediatric Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis through single-cell transcriptomics," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62090-5
    DOI: 10.1038/s41467-025-62090-5
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