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). (November 2020)

• Record Type: Journal Article
• Authors: Mizukawa, Y.; Kimishima, M.; Aoyama, Y.; Shiohara, T.
• Is Part Of: International journal of infectious diseases. Volume 100(2020)
• Page Start: 239
• Page End: 246
• Publication Date: 2020-11
• Subjects: cMOs classical monocytes -- CMV cytomegalovirus -- CRP C-reactive protein -- DDS score drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic syndrome severity score -- DiHS/DRESS drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic syndrome -- IFN interferon -- IL interleukin -- IRIS immune reconstitution inflammatory syndrome -- GVHD graft-versus-host disease -- pMOs pro-inflammatory monocytes -- TNF tumor necrosis factor -- TARC thymus and activation-regulated chemokine -- Tregs regulatory T cells; Biomarkers -- Cytokine/chemokine -- Cytomegalovirus -- Drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic syndrome (DRESS) -- Immune reconstitution inflammatory syndrome (IRIS); Communicable diseases -- Periodicals; Communicable Diseases -- Periodicals; Communicable diseases; Periodicals; Electronic journals; 616.9
• DOI: 10.1016/j.ijid.2020.08.078
• Languages: English
• ISSNs: 1201-9712

Abstract

Highlights: CMV reactivation in immunosuppressive settings is associated with fatal outcomes. CMV reactivation is associated with fatal complications in severe drug reactions. Monocyte-derived cytokines and Tregs are useful biomarkers for CMV reactivation. Increased biomarker levels at baseline are blunted by systemic corticosteroids. CMV reactivation can be predictable and preventable by using our algorithm. 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 three 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 the onset of CMV reactivation; the use of corticosteroids obscured the large differences in these cytokines at baseline. CMV-positive cases were found to have normal Tregs frequencies at baseline, while negative cases had 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 an accurate association with CMV reactivation.