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Exacerbating effects of circadian rhythm disruption on the systemic lupus erythematosus

Luping Shen1, Mo Han1, Xuan Luo1

  • 1Key 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.

Lupus Science & Medicine
|April 10, 2024
PubMed

Insights

Circadian rhythm disruption (CRD) is linked to systemic lupus erythematosus (SLE) flares and lupus nephritis. Genetic markers of CRD can predict SLE exacerbation, highlighting CRD

Area of Science:

  • Immunology and Genetics
  • Chronobiology
  • Systemic Lupus Erythematosus (SLE) Research

Background:

  • Circadian rhythm disruption (CRD) is associated with inflammation and immune disorders.
  • The specific role of CRD in the progression of systemic lupus erythematosus (SLE), particularly lupus nephritis (LN), remains largely uncharacterized.
  • Understanding the interplay between circadian rhythms, immune function, and SLE pathogenesis is crucial for developing predictive biomarkers.

Purpose of the Study:

  • To investigate the impact of circadian rhythms on immune function and inflammation in SLE.
  • To determine the contribution of CRD to SLE progression, specifically towards lupus nephritis (LN).
  • To identify potential biomarkers for predicting SLE exacerbation based on circadian rhythm characteristics.

Main Methods:

  • Retrospective analysis of clinical characteristics and transcriptional profiles from 373 samples.
  • Application of bioinformatics and machine-learning techniques to identify disease-related patterns.
  • Development of a flare risk score (FRS) for predicting SLE progression and utilization of Mendelian randomization for causal inference.

Main Results:

  • Abnormalities in the circadian pathway were detected in SLE patients, with lower enrichment correlating with disease state (normalized enrichment score=0.6714, p=0.0062).
  • CRD was strongly linked to lupus flares; the FRS demonstrated significant predictive ability for disease progression (5-year AUC: 0.76), further improved by a prognostic nomogram (AUC=0.77).
  • Mendelian randomization revealed an inverse causal relationship between CRD and SLE (OR 0.6284, p=0.0485) and a positive causal relationship with glomerular disorders (OR 0.0337, p=0.0280).

Conclusions:

  • Genetic signatures associated with CRD can serve as effective biomarkers for predicting SLE exacerbation.
  • CRD plays a significant role in the progression of SLE, including the development of lupus nephritis.
  • These findings underscore the importance of considering circadian rhythm health in SLE management and prognosis.
Abstract

Keywords:
inflammationlupus nephritisrisk factorssystemic lupus erythematosus

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