Enhancing lupus outcomes by means of biology beyond overt clinical features, exemplified in an in-depth investigation of the effects of circadian rhythm disruption

Abstract

SLE is a complex autoimmune disease, characterised by a prominent clinical heterogeneity,1 with lupus nephritis (LN) standing as one of its most severe manifestations.2 Despite significant advances in understanding SLE pathogenesis, the precise role of circadian rhythm disruption (CRD) in SLE and particularly its link to LN has remained elusive. In this issue of Lupus Science and Medicine , we are presented with a thought-provoking study by Shen et al , shedding new light on the intricate interplay between circadian rhythms and SLE severity.3 What sets this study apart is its comprehensive exploration of the impact of circadian rhythms on immune function and inflammation in the context of SLE. The authors embarked on a retrospective analysis, delving into clinical characteristics and transcriptional profiles of a large number of samples using advanced bioinformatics and machine learning methodologies. Through meticulous analysis, they uncovered compelling evidence of abnormalities within the circadian pathway in patients with SLE, indicating a potential link with the disease or disease states. Notably, the authors’ findings unveil an association between CRD and lupus flares, potentially implicating a role for CRD in disease evolution. Central to the authors’ investigation is the introduction of a Flare Risk Score (FRS), a tool designed to predict overall disease progression in patients with SLE. The FRS, developed through a rigorous analytical pipeline, exhibited good ability to forecast disease severity, offering a novel approach …