Rheumatology and Immunology Center, China Medical University Hospital, Taichung, Taiwan.
College of Medicine, China Medical University, Taichung, Taiwan.
Front Immunol. 2021 Jul 23;12:719544. doi: 10.3389/fimmu.2021.719544. eCollection 2021.
Hyperinflammation with dysregulated production of galectins and cytokines may develop in COVID-19 or adult-onset Still's disease (AOSD). Given the similar clinical features in both diseases, it is necessary to identify biomarkers that can differentiate COVID-19 from AOSD. However, the related data remain scarce currently.
In this cross-sectional study, plasma levels of galectin-3, galectin-9, and soluble TIM-3 (sTIM-3) were determined by ELISA in 55 COVID-19 patients (31 non-severe and 24 severe), 23 active AOSD patients, and 31 healthy controls (HC). The seropositivity for SARS-CoV-2 was examined using an immunochromatographic assay, and cytokine profiles were determined with the MULTIPLEX platform.
Significantly higher levels of galectin-3, galectin-9, IL-1β, IL-1Ra, IL-10, IFN-α2, IL-6, IL-18, and TNF-α were observed in severe COVID-19 and active AOSD patients compared with HC (all p<0.001). AOSD, but not COVID-19, showed significantly higher IFN-γ and IL-17A compared with HC (both p<0.01). Moreover, active AOSD patients had 68-fold higher IL-18 levels and 5-fold higher ferritin levels than severe COVID-19 patients (both p<0.001). IL-18 levels at the cut-off value 190.5pg/mL had the highest discriminative power for active AOSD and severe COVID-19, with AUC 0.948, sensitivity 91.3%, specificity 95.8%, and accuracy of 91.5% (p<0.005). Multivariate regression analysis revealed IL-18 as a significant predictor of active AOSD (p<0.05).
Active AOSD patients share features of hyperinflammation and cytokine storm with severe COVID-19 patients but possess a distinct cytokine profile, including elevated IL-18, IL-6, IFN-γ, and IL-17A. IL-18 is a potential discriminator between AOSD and COVID-19 and may significantly predict active AOSD.
COVID-19 或成人Still 病（AOSD）可能会出现过度炎症和调节失常的半乳糖凝集素和细胞因子的产生。鉴于这两种疾病的临床特征相似，有必要确定能够区分 COVID-19 和 AOSD 的生物标志物。然而，目前相关数据仍然很少。
在这项横断面研究中，通过 ELISA 测定了 55 例 COVID-19 患者（31 例非重症和 24 例重症）、23 例活动性 AOSD 患者和 31 名健康对照者（HC）的血浆半乳糖凝集素-3、半乳糖凝集素-9 和可溶性 TIM-3（sTIM-3）水平。使用免疫层析法检测 SARS-CoV-2 的血清阳性率，并使用 MULTIPLEX 平台测定细胞因子谱。
与 HC 相比，重症 COVID-19 和活动性 AOSD 患者的半乳糖凝集素-3、半乳糖凝集素-9、IL-1β、IL-1Ra、IL-10、IFN-α2、IL-6、IL-18 和 TNF-α水平显著升高（均 p<0.001）。与 HC 相比，AOSD 而非 COVID-19 患者的 IFN-γ和 IL-17A 水平显著升高（均 p<0.01）。此外，活动性 AOSD 患者的 IL-18 水平比重症 COVID-19 患者高 68 倍，铁蛋白水平高 5 倍（均 p<0.001）。IL-18 水平截断值 190.5pg/mL 对活动性 AOSD 和重症 COVID-19 具有最高的区分能力，AUC 为 0.948，灵敏度为 91.3%，特异性为 95.8%，准确性为 91.5%（p<0.005）。多变量回归分析显示，IL-18 是活动性 AOSD 的显著预测因子（p<0.05）。
活动性 AOSD 患者与重症 COVID-19 患者具有相似的过度炎症和细胞因子风暴特征，但具有独特的细胞因子谱，包括升高的 IL-18、IL-6、IFN-γ和 IL-17A。IL-18 可能是 AOSD 和 COVID-19 之间的潜在鉴别因子，并可能显著预测活动性 AOSD。
