Circadian Rhythm–Related Genes in Autoimmune Diseases: A Multiomics Scoping Review

ABSTRACT Background: The circadian clock regulates immune and metabolic homeostasis through transcriptional–translational feedback loops involving CLOCK, BMAL1, PER, CRY, REV-ERB, and ROR. Disruption of these rhythms contributes to immune dysregulation and has been implicated in the pathogenesis of autoimmune diseases. Objective: This scoping review maps multiomics evidence on circadian rhythm–related genes in autoimmune diseases and identifies gaps to guide future chrono-immunology studies. Methods: Following the PRISMA-ScR framework, PubMed, Scopus, Cochrane Library, Springer Nature, and ClinicalTrials.gov were searched without date restrictions. Eligible studies included genomic, transcriptomic, epigenomic, proteomic, or metabolomic analyses investigating circadian gene dysregulation in autoimmune contexts. Results: Twelve studies met inclusion criteria, encompassing systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), multiple sclerosis (MS), psoriatic arthritis (PsA), Graves’ disease, and epidermolysis bullosa acquisita (EBA). Across omics layers, BMAL1, PER, CRY, REV-ERBα, and RORα were frequently dysregulated, influencing leukocyte activation, cytokine rhythms, and metabolic pathways. Key findings include BMAL1 suppression correlating with SLE activity, RORα regulating Th17 differentiation, and inflammatory arthritis reprogramming hepatic ceramide rhythmicity. Epigenomic data further revealed CEBP-mediated methylation in Ssc and HLA-DQB1 methylation in PsA. Conclusions: Multiomics evidence supports a reciprocal relationship between circadian and immune systems, where rhythm disruption both drives and responds to inflammation. Time-resolved and integrative studies are needed to define disease-specific circadian signatures and develop chronotherapeutic strategies targeting core clock regulators such as RORα and REV-ERBα. These findings underscore the potential of circadian biomarkers in refining patient stratification and suggest that aligning immunomodulatory therapies with biological rhythms could enhance clinical outcomes. Keywords: circadian rhythm, autoimmunity, multiomics, BMAL1, RORα, chrono-inflammation, chronotherapy.