Background Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe adverse drug eruption associated with human herpesvirus 6 (HHV-6). HHV-6 has been shown to encode four viral microRNAs (miRNAs): hhv6b-miR-Ro6-1, -2, -3 and -4; however, their precise roles in the regulation of HHV-6 latency and reactivation as well as their expression in the context of human diseases including DIHS/DRESS remain largely unknown.
Objectives To investigate the expression of HHV-6-derived miRNAs in the serum of DIHS/DRESS patients during the acute and subacute stages.
Methods Ten patients with DIHS/DRESS, 10 with maculopapular exanthema (MPE), and 10 healthy controls were enrolled. Serum was isolated and the expression levels of the four HHV-6 miRNAs were measured using a real-time polymerase chain reaction (PCR).
Results The maximum levels of hhv6b-miR-Ro6-1, -2, -3, and -4 in serum were significantly higher in DIHS/DRESS patients than in MPE patients and healthy controls. Serum levels of hhv6b-miR-Ro6-2 were increased before or at the same time as the detection of HHV-6 DNA, while those of hhv6b-miR-Ro6-1 and/or -4 were increased a few weeks later than the expression of hhv6b-miR-Ro-2 in some DIHS/DRESS patients. Serum levels of hhv6b-miR-Ro6-1, -2, and -3 correlated with the RegiSCAR-Group Diagnosis Score for DRESS (DRESS score). Serum levels of hhv6b-miR-Ro6-2 and -3 correlated with the duration of fever (>38.0°C).
Conclusions Hhv6b-miR-Ro6-2 may be an early and specific biomarker for predicting the reactivation of HHV-6. The up-regulation of HHV-6-derived miRNAs may reflect the reactivation of HHV-6 and disease severity.

HHV-6-derived microRNAs in the serum/PBMC of DIHS/DRESS patients