Department of Pediatrics, Changhua Christian Children Hospital, Taiwan; School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan.
J Invest Dermatol. 2019 Aug;139(8):1722-1731. doi: 10.1016/j.jid.2018.10.048. Epub 2019 Feb 5.
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 ST2ILC2s 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.
药物反应伴嗜酸性粒细胞增多和全身性症状（DRESS）综合征是一种危及生命的疾病，估计死亡率为 2%。最近，II 型固有淋巴细胞（ILC2）被认为是过敏疾病发病机制的重要贡献者。然而，ILC2 和 ILC2 相关细胞因子在 DRESS 中的作用尚不清楚。在此，我们纳入了 54 名参与者（包括 24 名 DRESS 综合征患者和 30 名健康对照者），并在皮肤损伤/血液中鉴定出增加的 ST2ILC2 群体。此外，DRESS 患者的急性阶段血清可溶性 ST2（sST2）、IL-5 和 TSLP 水平显著升高。在激素治疗后，观察到 ILC2 群体、血清 sST2 和 IL-5 减少，皮疹、嗜酸性粒细胞增多和丙氨酸氨基转移酶改善。在迟发反应者组（n=13）中，急性阶段血清 IL-33、sST2、IL-5 和 TSLP 水平显著升高，但只有 sST2 水平与丙氨酸氨基转移酶和嗜酸性粒细胞改善在 4 周随访时相关。血清 sST2 水平也与 IL-33（ρ=0.49；P=0.02）和丙氨酸氨基转移酶水平（ρ=0.65；P<0.01）相关在 DRESS 发作时。我们的研究结果表明，ILC2 细胞中高表达的 IL-33/ST2 参与药物超敏反应的皮肤炎症，血清 sST2 水平可作为预测 DRESS 综合征患者肝受累的潜在生物标志物。
