miRNA-375 Combined EB-DNA as Differential Diagnostic Biomarker for EBV-IM and EBV-HLH in Children

In children, Epstein-Barr Virus (EBV) often causes infectious mononucleosis (EBV-IM) but can escalate to a severe condition called EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). Differentiating these conditions is vital for proper treatment and prognosis. This study aimed to find plasma biomarkers to distinguish between EBV-IM and EBV-HLH. A retrospective analysis was performed on 17 children with EBV-IM and 23 with EBV-HLH. Selected microRNAs (miRNAs) were measured in plasma using qPCR, and EBV DNA was isolated and quantified. Biomarker effectiveness was assessed using constructing receiver operating characteristic (ROC) curves and the area under the curve (AUC) calculations. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed a significant enrichment of miR-375, miR-148a-3p, and miR-92a-1-5p within the Viral Carcinogenesis pathway. Quantitative PCR validation demonstrated a marked upregulation of miR-375 and miR-148a-3p in patients with EBV-HLH compared to those with EBV-IM, whereas the expression of miR-92a-1-5p did not show a statistically significant difference between the groups. Notably, receiver operating characteristic (ROC) analysis indicated that the combined evaluation of miR-375 and EBV-DNA load achieved superior diagnostic discrimination between EBV-HLH and EBV-IM, with an AUC of 0.951, highlighting its potential high clinical utility. The integrated biomarker panel, consisting of miR-375 and EBV-DNA load, demonstrated high diagnostic accuracy in distinguishing between EBV-HLH and EBV-IM. These findings offer a clinically applicable tool for precise differential diagnosis and therapeutic stratification.