The interferon-γ-induced protein 10/CXCR3 axis is associated with human herpesvirus-6 reactivation and the development of sequelae in drug reaction with eosinophilia and systemic symptoms
Journal
British Journal of Dermatology
Date Issued
2020
Author(s)
Abstract
Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a condition caused by a drug-induced immune response. Previous reports have found that CXCL10, also known as interferon-γ-induced protein (IP)-10, may participate in the pathogenesis of cutaneous adverse drug reactions. However, the exact role of IP-10 in DRESS and Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) has remained unknown. Objectives: This comparative prospective cohort study aimed to ascertain the roles of the IP-10/CXCR3 axis in DRESS and SJS/TEN. Methods: Plasma IP-10 levels were analysed, and univariate analyses were conducted to assess the relationship between IP-10, human herpesvirus (HHV)-6 reactivation and the development of long-term sequelae. We also performed immunohistochemical staining using skin specimens and flow cytometry to determine the expression of CXCR3 in peripheral blood mononuclear cells (PBMCs). Results: Significantly higher plasma IP-10 levels were observed in patients with DRESS with long-term sequelae (effect size 0·81) and also in those with HHV-6 reactivation (effect size 0·83). By immunohistochemistry, more abundant IP-10+ and CXCR3+ cells were demonstrated in the skin lesions of patients with DRESS with HHV-6 reactivation. The percentages of CLA+?CXCR3+?CD4+ cells and CLA+?CXCR3+?CD8+ cells were also higher in the PBMCs of HHV-6-reactivated patients with DRESS than in those of patients with SJS/TEN. Conclusions: Higher plasma IP-10 levels are associated with the development of long-term sequelae in DRESS. Higher IP-10/CXCR3 expression in skin and more abundant CLA+?CXCR3+?CD4+ cells and CLA+?CXCR3+?CD8+ cells were observed in patients with DRESS with HHV-6 reactivation. The IP-10/CXCR3 axis is associated with HHV-6 reactivation and development of long-term sequelae in DRESS. What is already known about this topic?. Elevated levels of interferon-γ-induced protein-10 (IP-10) have been observed in patients with drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Patients with DRESS tend to develop long-term autoimmune sequelae, including type 1 diabetes and autoimmune thyroiditis. IP-10 has been associated with these autoimmune diseases in previous studies. What does this study add?. The patients with DRESS with HHV-6 reactivation exhibited higher levels of IP-10 in the plasma and skin than the patients with DRESS without HHV-6 reactivation and the patients with SJS/TEN. Patients with DRESS with higher plasma IP-10 levels tended to develop sequelae during long-term follow-up. What is the translational message?. IP-10 is a useful biomarker to predict the development of long-term sequelae in patients with DRESS. Linked Comment: Bello?n and Kardaun. Br J Dermatol 2020; 183:804–805. ? 2020 British Association of Dermatologists
SDGs
Other Subjects
allopurinol; anticonvulsive agent; beta lactam antibiotic; chemokine receptor CXCR3; dapsone; ferritin; gamma interferon inducible protein 10; immunoglobulin G; nonsteroid antiinflammatory agent; prednisolone; salazosulfapyridine; sulfamethoxazole; chemokine receptor CXCR3; CXCR3 protein, human; gamma interferon; adult; Article; cholestasis; chronic urticaria; clinical article; clinical feature; cohort analysis; comparative study; controlled study; disease severity; DRESS syndrome; end stage renal disease; female; ferritin blood level; flow cytometry; follow up; Hashimoto disease; human; human cell; Human herpesvirus 6; human tissue; immunohistochemistry; inflammatory cell; insulin dependent diabetes mellitus; male; middle aged; nonhuman; outcome assessment; peripheral blood mononuclear cell; priority journal; prospective study; protein blood level; skin biopsy; skin defect; Stevens Johnson syndrome; toxic epidermal necrolysis; virus reactivation; mononuclear cell; Stevens Johnson syndrome; Drug Hypersensitivity Syndrome; Herpesvirus 6, Human; Humans; Interferon-gamma; Leukocytes, Mononuclear; Prospective Studies; Receptors, CXCR3; Stevens-Johnson Syndrome
Publisher
Blackwell Publishing Ltd
Type
journal article