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Updated: Sep 4, 2026
Separation of Immune Cell Subpopulations in Peripheral Blood Samples from Children with Infectious Mononucleosis
Published on: September 7, 2022
Baseline plasma EBV-DNA load as an adjunctive biomarker for refractory or recurrent disease in pediatric EBV-HLH
Yu Furui1, Rintaro Ono2, Shohei Shigeto3
1Department of Pediatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
Background:
Quantitative Epstein-Barr virus (EBV)-DNA measurement is used in EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), but the optimal sample type for risk assessment and monitoring remains unclear.
Methods:
We retrospectively analyzed 71 pediatric patients with newly diagnosed EBV-HLH from a Japanese multicenter cohort between April 2019 and May 2025. EBV-DNA loads in plasma, white blood cells, and T- and B-cell fractions were centrally quantified by real-time polymerase chain reaction. Patients were classified into remission and refractory/recurrent (R/R) groups.
Results:
Baseline plasma EBV-DNA was higher in the R/R group than in the remission group (median, 5.762 vs. 5.366 log10 copies/mL; p = 0.024), whereas cellular EBV-DNA loads did not differ. A plasma cutoff of 5.560 log10 copies/mL showed modest discrimination for R/R disease (area under the curve, 0.667). Predominant EBV-detected cell fraction and baseline T-cell receptor (TCR) clonality were not associated with R/R, but TCR clonality at 2 weeks was more frequent in the R/R group (44.4% vs. 7.7%; p = 0.027). In remission cases, plasma EBV-DNA declined rapidly, whereas low-level EBV-DNA persisted in cellular compartments during follow-up.
Conclusions:
Baseline plasma EBV-DNA may serve as an adjunctive marker for disease assessment and monitoring in pediatric EBV-HLH, but not as a stand-alone predictor.
