Department of Rheumatology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Front Endocrinol (Lausanne). 2023 Jul 27;14:1164679. doi: 10.3389/fendo.2023.1164679. eCollection 2023.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a remarkable predominance in female, suggesting that steroid hormones may be involved in the pathogenesis. However, steroid signature of SLE patients has not been fully explored.
A metabolic profiling analysis based on gas chromatography/mass spectrometry (GC/MS) with high sensitivity and reproducibility was employed to comprehensively reveal SLE-specific steroid alterations.
More than 70 kinds of steroids in urine were detected by gas chromatography/mass spectrometry (GC/MS) to reveal SLE-specific steroid alterations. Principle component analysis demonstrated that the steroid profile was obviously distinguished between patients with SLE and controls. A lower level of total androgens was observed in patients, and nine androgens [dehydroepiandrosterone (DHEA), testosterone, Etio, androsterone, βαβ-Diol, Epi-An, Epi-DHT, 16α-OH-DHEA, and A-Diol] underwent significant decrease. Moreover, patients with SLE exhibited a slightly higher level of total estrogens than controls, and three estrogens (17-Epi-E3, 17α-E2, and E3) were remarkably increased. Furthermore, we identified the elevation of two sterols (Lan and Chol), and the reduction of one corticoid (11-DeoxyF) and two progestins (5α-DHP and 11β-OH-Prog) in patients.
In this study, metabolic signature of urinary steroids associated with SLE was comprehensively defined by GC/MS for the first time, and steroid metabolism disorders were found in patients with SLE, especially the conversion of androgens to estrogens. Our findings will provide new insights for a deeper understanding of the mechanism of steroid hormones in the pathogenesis of SLE and will help to unravel the reason of sexual disparity in SLE.
系统性红斑狼疮（SLE）是一种以女性为主的全身性自身免疫性疾病，这表明类固醇激素可能参与其发病机制。然而，SLE 患者的类固醇特征尚未得到充分探索。
采用基于气相色谱/质谱（GC/MS）的代谢组学分析方法，具有高灵敏度和重现性，全面揭示 SLE 特异性类固醇改变。
通过气相色谱/质谱（GC/MS）检测到尿液中 70 多种类固醇，以揭示 SLE 特异性类固醇改变。主成分分析表明，SLE 患者和对照组之间的类固醇谱明显不同。患者的总雄激素水平较低，9 种雄激素[脱氢表雄酮（DHEA）、睾酮、Etio 雄酮、βαβ-Diol、Epi-An、Epi-DHT、16α-OH-DHEA 和 A-Diol]显著降低。此外，SLE 患者的总雌激素水平略高于对照组，3 种雌激素（17-Epi-E3、17α-E2 和 E3）显著增加。此外，我们还发现患者体内两种甾醇（Lan 和 Chol）升高，一种皮质醇（11-DeoxyF）和两种孕激素（5α-DHP 和 11β-OH-Prog）减少。
本研究首次通过 GC/MS 全面定义了与 SLE 相关的尿类固醇代谢特征，并发现 SLE 患者存在类固醇代谢紊乱，特别是雄激素向雌激素的转化。我们的研究结果将为深入了解类固醇激素在 SLE 发病机制中的作用机制提供新的见解，并有助于揭示 SLE 中性别差异的原因。
