Key Laboratory of Drug Metabolism and Pharmacokinetics, Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.
Jiangsu Renocell Biotech Co Ltd, Nanjing, China.
Lupus Sci Med. 2024 Apr 9;11(1):e001109. doi: 10.1136/lupus-2023-001109.
Circadian rhythm disruption (CRD) has been associated with inflammation and immune disorders, but its role in SLE progression is unclear. We aimed to investigate the impact of circadian rhythms on immune function and inflammation and their contribution to SLE progression to lupus nephritis (LN).
This study retrospectively analysed the clinical characteristics and transcriptional profiles of 373 samples using bioinformatics and machine-learning methods. A flare risk score (FRS) was established to predict overall disease progression for patients with lupus. Mendelian randomisation was used to analyse the causal relationship between CRD and SLE progression.
Abnormalities in the circadian pathway were detected in patients with SLE, and lower enrichment levels suggested a disease state (normalised enrichment score=0.6714, p=0.0062). The disruption of circadian rhythms was found to be closely linked to lupus flares, with the FRS showing a strong ability to predict disease progression (area under the curve (AUC) of 5-year prediction: 0.76). The accuracy of disease prediction was improved by using a prognostic nomogram based on FRS (AUC=0.77). Additionally, Mendelian randomisation analysis revealed an inverse causal relationship between CRD and SLE (OR 0.6284 (95% CI 0.3630 to 1.0881), p=0.0485) and a positive causal relationship with glomerular disorders (OR 0.0337 (95% CI 1.634e-3 to 6.934e-1), p=0.0280).
Our study reveals that genetic characteristics arising from CRD can serve as biomarkers for predicting the exacerbation of SLE. This highlights the crucial impact of CRD on the progression of lupus.
昼夜节律紊乱（CRD）与炎症和免疫紊乱有关，但它在 SLE 进展中的作用尚不清楚。我们旨在研究昼夜节律对免疫功能和炎症的影响及其对 SLE 进展为狼疮肾炎（LN）的贡献。
本研究使用生物信息学和机器学习方法对 373 个样本的临床特征和转录谱进行了回顾性分析。建立了一个发作风险评分（FRS）来预测狼疮患者的总体疾病进展。孟德尔随机化用于分析 CRD 与 SLE 进展之间的因果关系。
在 SLE 患者中检测到昼夜节律途径异常，较低的富集水平表明疾病状态（归一化富集评分=0.6714，p=0.0062）。昼夜节律的破坏与狼疮发作密切相关，FRS 显示出很强的预测疾病进展的能力（5 年预测的 AUC：0.76）。使用基于 FRS 的预后列线图可提高疾病预测的准确性（AUC=0.77）。此外，孟德尔随机化分析显示 CRD 与 SLE 之间存在反向因果关系（OR 0.6284（95%CI 0.3630 至 1.0881），p=0.0485），与肾小球疾病之间存在正向因果关系（OR 0.0337（95%CI 1.634e-3 至 6.934e-1），p=0.0280）。
我们的研究表明，CRD 产生的遗传特征可作为预测 SLE 恶化的生物标志物。这凸显了 CRD 对狼疮进展的重要影响。
