Exacerbating effects of circadian rhythm disruption on the systemic lupus erythematosus
Objective 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...
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BMJ Publishing Group
2024-05-01
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| Series: | Lupus Science and Medicine |
| Online Access: | https://lupus.bmj.com/content/11/1/e001109.full |
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| author | Jing Wang Qing Liu Fang Zhou Guangji Wang Xuan Luo Ning Wei Luping Shen Mo Han Qixiang Zhang Huanke Xu |
| author_facet | Jing Wang Qing Liu Fang Zhou Guangji Wang Xuan Luo Ning Wei Luping Shen Mo Han Qixiang Zhang Huanke Xu |
| author_sort | Jing Wang |
| collection | DOAJ |
| description | Objective 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).Methods 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.Results 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).Conclusion 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. |
| format | Article |
| id | doaj-art-347c1b54e7a54fa084b93669816bd613 |
| institution | Kabale University |
| issn | 2053-8790 |
| language | English |
| publishDate | 2024-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Lupus Science and Medicine |
| spelling | doaj-art-347c1b54e7a54fa084b93669816bd6132024-11-10T07:05:08ZengBMJ Publishing GroupLupus Science and Medicine2053-87902024-05-0111110.1136/lupus-2023-001109Exacerbating effects of circadian rhythm disruption on the systemic lupus erythematosusJing Wang0Qing Liu1Fang Zhou2Guangji Wang3Xuan Luo4Ning Wei5Luping Shen6Mo Han7Qixiang Zhang8Huanke Xu9Department of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou, ChinaJiangsu Renocell Biotech Co Ltd, Nanjing, ChinaKey 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 ChinaKey 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 ChinaDepartment of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, ChinaJiangsu Renocell Biotech Co Ltd, Nanjing, ChinaKey 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 ChinaKey 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 ChinaKey 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 ChinaKey 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 ChinaObjective 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).Methods 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.Results 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).Conclusion 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.https://lupus.bmj.com/content/11/1/e001109.full |
| spellingShingle | Jing Wang Qing Liu Fang Zhou Guangji Wang Xuan Luo Ning Wei Luping Shen Mo Han Qixiang Zhang Huanke Xu Exacerbating effects of circadian rhythm disruption on the systemic lupus erythematosus Lupus Science and Medicine |
| title | Exacerbating effects of circadian rhythm disruption on the systemic lupus erythematosus |
| title_full | Exacerbating effects of circadian rhythm disruption on the systemic lupus erythematosus |
| title_fullStr | Exacerbating effects of circadian rhythm disruption on the systemic lupus erythematosus |
| title_full_unstemmed | Exacerbating effects of circadian rhythm disruption on the systemic lupus erythematosus |
| title_short | Exacerbating effects of circadian rhythm disruption on the systemic lupus erythematosus |
| title_sort | exacerbating effects of circadian rhythm disruption on the systemic lupus erythematosus |
| url | https://lupus.bmj.com/content/11/1/e001109.full |
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