High Epstein-Barr Virus DNA Load in T Cells Predicts Hemophagocytic Lymphohistiocytosis

Background To evaluate the risk of hemophagocytic lymphohistiocytosis (HLH) linked to Epstein-Barr virus (EBV) infection in different lymphocyte subtypes during infectious mononucleosis (IM). Methods Patients with IM and patients with EBV-HLH were included within the Children's Critical EBV Infection cohort for a nested case-control study. Lymphocytes were isolated into T, B, and natural killer cells using magnetic bead sorting, followed by individual polymerase chain reaction testing. Receiver operating characteristic curve analysis identified subtype-specific cutoffs for EBV-HLH prediction. Kaplan-Meier and Cox regression analyses assessed viral load-HLH risk associations. Results Patients with EBV-HLH exhibited significantly higher T-cell viral loads than patients with IM (median, 5.1 × 104 vs 6.0 × 102 copies/106 cells). A T-cell viral load >1.5 × 104 copies/106 cells was linked with higher incidences of viral sepsis, renal dysfunction, hepatic dysfunction, coagulation dysfunction, and cardiovascular dysfunction (odds ratios, 10.0, 4.7, 6.5, 15.7, and 6.5). This elevated T-cell viral load was a strong predictor for distinguishing EBV-HLH (AUC 0.815) and increased the risk of developing EBV-HLH (hazard ratio 4.7). Conclusions High EBV DNA load in T cells can serve as a potential predictor for the development of EBV-HLH.