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. 2025 Jan 30;73(1):43.
doi: 10.1007/s12026-025-09597-7.

The ability of CD4dimCD8+ T cells to distinguish between Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis and pediatric infectious mononucleosis

Can Liu  1 , Aijun Zou  1 , Xianyu Wang  1 , Caizhi Huang  2
Affiliations

The ability of CD4dimCD8+ T cells to distinguish between Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis and pediatric infectious mononucleosis

Can Liu et al. Immunol Res. .

Abstract

Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (EBV-HLH) and infectious mononucleosis (IM) are characterized by fever, hepatomegaly, and splenomegaly, but HLH has a 50% lethality rate. Therefore, this study aimed to compare the laboratory findings in differentiating EBV-HLH children from IM children who have fever, hepatomegaly, or splenomegaly. A total of 131 IM patients and 29 EBV-HLH pediatric patients with fever, hepatomegaly, or splenomegaly were enrolled in our study. The clinical traits and laboratory findings were analyzed, and a predictive regression analysis was also performed. EBV-HLH patients had a lower set of diagnostic markers, which included fibrinogen (FIB), white blood cells (WBC), hemoglobin (Hb), and platelet (PLT), compared to IM patients. Triglyceride (TG) and ferritin were elevated obviously in EBV-HLH patients compared to IM patients. CD4dimCD8+ T cells are highly activated T cells. EBV-HLH patients experienced a significant decrease in the absolute number and ratio of CD4dimCD8+T cells (CD4dimCD8+T#, CD4dimCD8+T%) compared to IM patients in our study. The AUC of CD4dimCD8+ T # in the diagnosis of EBV-HLH was 0.920 with a sensitivity of 86.2% and a specificity of 90.1%. A logistic regression analysis was developed to improve sensitivity. The results revealed that lower levels of Hb, FIB, and CD4dimCD8+T cells were risk factors for EBV-HLH. The regression model for separating EBV-HLH from EBV-IM had an AUC of was 0.996 with a sensitivity of 100% and a specificity of 95.3%. The ratio and absolute number of CD4dimCD8+T cells were decreased in IM and EBV-HLH patients. EBV-HLH can be identified in IM patients with fever, hepatomegaly, or splenomegaly by detecting Hb, FIB, and the absolute number of CD4dimCD8+T cells.

Keywords: CD4dimCD8+T cells; Fibrinogen; Hemoglobin; Hemophagocytic lymphohistiocytosis; Infectious mononucleosis.

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Conflict of interest statement

Declarations. Ethics approval: The study was approved by the local ethics committee of Hunan Children’s Hospital (Code: HCHLL-2024–471). Conflict of interest: The authors declare no competing interests.

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References

    1. Thompson MP, Kurzrock R. Epstein-Barr virus and cancer. Clin Cancer Res. 2004;10:803–21. https://doi.org/10.1158/1078-0432.ccr-0670-3 . - DOI - PubMed
    1. Womack J, Jimenez M. Common questions about infectious mononucleosis. Am Fam Physician. 2015;91:372–6. - PubMed
    1. Smith MC, Cohen DN, Greig B, et al. The ambiguous boundary between EBV-related hemophagocytic lymphohistiocytosis and systemic EBV-driven T cell lymphoproliferative disorder. Int J Clin Exp Pathol. 2014;7:5738–49. - PubMed - PMC
    1. Smits BM, van Montfrans J, Merrill SA, et al. A minimal parameter set facilitating early decision-making in the diagnosis of hemophagocytic lymphohistiocytosis. J Clin Immunol. 2021;41:1219–28. https://doi.org/10.1007/s10875-021-01005-7 . - DOI - PubMed - PMC
    1. El-Mallawany NK, Curry CV, Allen CE. Haemophagocytic lymphohistiocytosis and Epstein-Barr virus: a complex relationship with diverse origins, expression and outcomes. Br J Haematol. 2022;196:31–44. https://doi.org/10.1111/bjh.17638 . - DOI - PubMed

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