Doctoral Program in Medical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Andalas, Padang, Indonesia; Department of Clinical Pharmacology, Dr. M. Djamil General Hospital, Padang, Indonesia.
Department of Pharmacology and Therapeutic, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Eur J Pharmacol. 2023 Mar 15;943:175555. doi: 10.1016/j.ejphar.2023.175555. Epub 2023 Jan 30.
The effect of corticosteroid therapy in COVID-19 patients is mediated by its suppressive effect on the regulations of inflammatory response. However, its clinical outcome is often unpredictable. This study aimed to explore the role of glucocorticoid receptors in corticosteroid response in Moderate-Severe COVID-19 patients. In this cross-sectional study, we attempted to find the relationship between the expression of the glucocorticoid receptor (encoded by NR3C1), the variation of glucocorticoid receptors isoform, and the mutations of glucocorticoid receptors exon with clinical response to corticosteroids. In addition, the relationship between glucocorticoid receptors expression and the expression of IκBα (encoded by NFKBIA) and glucocorticoid-induced leucine zipper protein (GILZ; encoded by TSC22D3) as steroid pathways was also evaluated. Thirty-four COVID-19 patients were studied. Blood was drawn before and on day 5 of corticosteroid treatment. Glucocorticoid receptors expression, isoform, and mutation were determined by RNA sequencing from white blood cells. Based on the improvement of clinical and oxygen status, patients were classified into responder and non-responder groups. Of thirty-four patients, 23 (67.6%) showed excellent responses to corticosteroids, and 11 (32.4%) were non-responders. The NR3C1 gene expression was significantly higher in the responsive group at baseline and after five days of glucocorticoid treatment. Isoform variant and mutation of glucocorticoid receptors did not correlate with clinical response. The expression of IκBα and GILZ correlated positively with glucocorticoid receptors expression. This study elucidates the relationship between glucocorticoid receptor expression with therapeutic responses to corticosteroids in moderate-severe COVID-19.
糖皮质激素治疗 COVID-19 患者的效果是通过其对炎症反应调节的抑制作用介导的。然而，其临床疗效往往不可预测。本研究旨在探讨糖皮质激素受体在中度至重度 COVID-19 患者中糖皮质激素反应中的作用。在这项横断面研究中，我们试图找到糖皮质激素受体（由 NR3C1 编码）的表达、糖皮质激素受体同工型的变化以及糖皮质激素受体外显子的突变与对皮质类固醇的临床反应之间的关系。此外，还评估了糖皮质激素受体表达与类固醇途径中 IκBα（由 NFKBIA 编码）和糖皮质激素诱导亮氨酸拉链蛋白（由 TSC22D3 编码）表达之间的关系。研究了 34 名 COVID-19 患者。在皮质类固醇治疗前和第 5 天采集血液。通过从白细胞中进行 RNA 测序来确定糖皮质激素受体的表达、同工型和突变。根据临床和氧合状态的改善，将患者分为应答者和非应答者组。在 34 名患者中，23 名（67.6%）对皮质类固醇有极好的反应，11 名（32.4%）无反应。在基线和糖皮质激素治疗 5 天后，NR3C1 基因表达在有反应组中明显更高。糖皮质激素受体的同工型变异和突变与临床反应无关。IκBα 和 GILZ 的表达与糖皮质激素受体表达呈正相关。本研究阐明了糖皮质激素受体表达与中度至重度 COVID-19 患者对皮质类固醇治疗反应之间的关系。
