Increased Type 2 Innate Lymphoid Cells in Patients with Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a life-threatening disorder with an estimated mortality rate of 2%. Recently, type II innate lymphoid cells (ILC2s) have been implicated as an important contributor to the pathogenesis of allergic disorders. However, the roles of ILC2s and ILC2-associated cytokines in DRESS remain unclear. Herein, we enrolled 54 participants (including 24 patients with DRESS syndrome and 30 healthy controls), and identified the increased ST2⁺ILC2s population in skin lesions/blood. In addition, serum soluble ST2 (sST2), IL-5, and TSLP levels were significantly elevated at the acute stage of patients with DRESS. Decreased ILC2s population, serum sST2, and IL-5, accompanied with rash, eosinophilia, and alanine aminotransferase improvement were observed after steroid treatment. In the delayed-responders group (n = 13), serum IL-33, sST2, IL-5, and TSLP levels were significantly increased at the acute phase, but only sST2 levels correlated with alanine aminotransferase and eosinophil improvement at the 4-week follow-up visit. Serum sST2 levels were also correlated with IL-33 (ρ = 0.49; P = 0.02) and alanine aminotransferase levels (ρ = 0.65; P < 0.01) at the onset of DRESS. Our results demonstrated high IL-33/ST2 expression in ILC2 cells plays a role in skin inflammation of drug hypersensitivity, and serum sST2 levels can be as a potential biomarker to predict liver involvement in patients with DRESS syndrome.