Epstein–Barr Virus DNA Detection Without Detectable Expression of Selected Viral Transcripts in Pediatric Patients with Systemic Lupus Erythematosus

Background: Epstein–Barr virus (EBV) has long been linked to systemic lupus erythematosus (SLE), mainly through molecular mimicry, altered B-cell biology, defective antiviral immune surveillance and intermittent viral reactivation. However, the detection of EBV DNA in clinical samples does not necessarily indicate transcriptionally active infection or direct viral modulation of host pathways. Methods: Peripheral blood samples from 39 pediatric patients with SLE and 29 healthy controls were analyzed for host immune and apoptotic gene expression, including NFKB1, IL10, TLR3, BCL2, BAX and CASP3. EBV DNA was assessed in both patients and controls. In EBV DNA-positive SLE samples, the expression of EBV transcripts representative of latent, lytic and immunomodulatory programs, including LMP1, EBNA1, BZLF1, and viral IL-10, was also evaluated. Host gene expression was additionally compared between EBV DNA-positive and EBV DNA-negative patients with SLE. Results: EBV DNA was detected in 8 of 39 patients with SLE (20.5%) and in none of the 29 healthy controls (0%; Fisher’s exact test, p = 0.0171). None of the EBV DNA-positive samples showed detectable expression of LMP1, EBNA1, BZLF1 or viral IL-10. Compared with healthy controls, patients with SLE showed increased CASP3 expression that remained significant after FDR correction, whereas the reduction in IL10 expression was nominally significant only in the unadjusted analysis. NFKB1, TLR3, BCL2, and BAX did not differ significantly. In the exploratory comparison between EBV DNA-positive and EBV DNA-negative patients with SLE, no host gene remained significantly associated with EBV DNA status after false discovery rate correction. Conclusions: EBV DNA was detected more frequently in patients with SLE than in healthy controls, but this finding was not accompanied by detectable expression of the selected EBV transcripts under the analytical conditions used or by a consistent host transcriptional signature associated with EBV DNA positivity. These findings emphasize the importance of distinguishing EBV DNA detection from detectable viral transcript expression in SLE.