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Single-Cell Transcriptomic Analysis of Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis.

Authors :
Suzuki, Takako
Sato, Yoshitaka
Okuno, Yusuke
Torii, Yuka
Fukuda, Yuto
Haruta, Kazunori
Yamaguchi, Makoto
Kawamura, Yoshiki
Hama, Asahito
Narita, Atsushi
Muramatsu, Hideki
Yoshikawa, Tetsushi
Takahashi, Yoshiyuki
Kimura, Hiroshi
Ito, Yoshinori
Kawada, Jun-ichi
Source :
Journal of Clinical Immunology. Apr2024, Vol. 44 Issue 4, p1-12. 12p.
Publication Year :
2024

Abstract

Epstein-Barr virus (EBV) infection can lead to infectious mononucleosis (EBV-IM) and, more rarely, EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), which is characterized by a life-threatening hyperinflammatory cytokine storm with immune dysregulation. Interferon-gamma (IFNγ) has been identified as a critical mediator for primary HLH; however, the detailed role of IFNγ and other cytokines in EBV-HLH is not fully understood. In this study, we used single-cell RNA sequencing to characterize the immune landscape of EBV-HLH and compared it with EBV-IM. Three pediatric patients with EBV-HLH with different backgrounds, one with X-linked lymphoproliferative syndrome type 1 (XLP1), two with chronic active EBV disease (CAEBV), and two patients with EBV-IM were enrolled. The TUBA1B + STMN1 + CD8 + T cell cluster, a responsive proliferating cluster with rich mRNA detection, was explicitly observed in EBV-IM, and the upregulation of SH2D1A—the gene responsible for XLP1—was localized in this cluster. This proliferative cluster was scarcely observed in EBV-HLH cases. In EBV-HLH cases with CAEBV, upregulation of LAG3 was observed in EBV-infected cells, which may be associated with an impaired response by CD8 + T cells. Additionally, genes involved in type I interferon (IFN) signaling were commonly upregulated in each cell fraction of EBV-HLH, and activation of type II IFN signaling was observed in CD4 + T cells, natural killer cells, and monocytes but not in CD8 + T cells in EBV-HLH. In conclusion, impaired responsive proliferation of CD8 + T cells and upregulation of type I IFN signaling were commonly observed in EBV-HLH cases, regardless of the patients’ background, indicating the key features of EBV-HLH. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
02719142
Volume :
44
Issue :
4
Database :
Academic Search Index
Journal :
Journal of Clinical Immunology
Publication Type :
Academic Journal
Accession number :
178055815
Full Text :
https://doi.org/10.1007/s10875-024-01701-0