Predictive biomarkers for cytomegalovirus reactivation before and after immunosuppressive therapy: A single-institution retrospective long-term analysis of patients with drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic syndrome (DRESS)

Abstract Objectives Cytomegalovirus (CMV) reactivation in patients with severe drug eruption on immunosuppressive therapy often leads to fulminant disease and even mortality, yet there are no biomarkers to accurately predict CMV reactivation either before or after immunosuppressive therapy. We aimed to assess whether patients who develop CMV reactivation (CMV-positive cases) have distinct immunological profiles from CMV-negative cases before and after immunosuppressive therapy. Methods We performed serial cytokine/chemokine and regulatory T cells (Tregs) assessments of 45 patients with drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic syndrome (DRESS) during a follow-up period of nearly 3 years after onset. Results Elevated IL-8, IL-10, IL-12p40, IL-15, TNF-α, G-CSF and MIP-1α levels at baseline were associated with later development of CMV reactivation, while after starting treatment IL-10 and IL-15 levels were associated with onset of CMV reactivation; use of corticosteroids obscured the large differences in these cytokines at baseline. CMV-positive cases were found to have normal frequencies of Tregs at baseline while negative cases had the elevated frequencies. Higher eotaxin, IL-10 and G-CSF levels and lower IL-12p40 levels at baseline might be used for predicting the development of lethal CMV disease. Conclusions The algorithm based on these results showed accurate association with CMV reactivation.