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• W4292657732 abstract "Abstract Background Why Epstein–Barr virus-related hemophagocytic lymphohistiocytosis (EBV-HLH) undergoes remission shortly after treatment and relapses rapidly and whether EBV infection in natural killer (NK)/T cells contributes to the deterioration of EBV-HLH are unknown. Methods EBV cell tropism and anti-EBV host cellular immunity were compared based on multicolor flow cytometry technique between EBV-HLH survivors and those who died to explore the key factors associated with the deterioration of HLH progression. Transcriptomics was performed to reveal the underlying mechanisms of EBV-HLH deterioration. Results In the deceased cases, EBV infection spread to NK (CD3-CD56+, 84.3%) and/or NKT (CD3 + CD56+, 67.9%) cells with a highly proliferating profile, whereas the infection was only limited to B cells in survivors. Although a similar low NK activation (< 1,000/million peripheral blood mononuclear cells) was observed at hospital admission, deceased cases had higher levels of NK cell degranulation (5,250 and 73,905 CD107a + NK cells for patients 1 and 2, respectively) and NK cytotoxicity and higher levels of EBV-specific CD4 + and CD8 + T cell response than survivors at the deterioration timepoint. Meanwhile, no cytokine storm was observed in the deceased cases at the deterioration phase. Interestingly, EBV-infected NK and NKT cells presented a higher percentage of copy number variations and significantly higher enrichment in canonical cancer pathways than noninfected cells, such as genes associated with proto-oncogene transcription factor ( Myc ), proliferation ( MKI67 ), and EBV LMP1-related carcinogenesis ( TRAF2 and Jak3 ) genes. Conclusions Our study suggest that the oncogenicity of EBV-infected NK/NKT cells deteriorates EBV-HLH, and the spread of EBV to NK and NKT cells may indicate a prephase of NK/T lymphoma. Thus, the findings of this study may guide future therapeutic strategies for EBV-HLH." @default.
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• W4292657732 date "2022-08-22" @default.
• W4292657732 modified "2023-09-28" @default.
• W4292657732 title "Oncogenicity of EBV-infected natural killer T cells deteriorate EBV-related hemophagocytic lymphohistiocytosis" @default.
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• W4292657732 doi "https://doi.org/10.21203/rs.3.rs-1970948/v1" @default.
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