Circadian rhythm in systemic autoimmune conditions: Potential of chrono-immunology in clinical practice: A narrative review

Abstract

The circadian rhythm (CR) is a fundamental biological process regulated by the Earth’s rotation and solar cycles. It plays a critical role in various bodily functions, and its dysregulation can have systemic effects. These effects impact metabolism, redox homeostasis, cell cycle regulation, gut microbiota, cognition, and immune response. Immune mediators, cycle proteins, and hormones exhibit circadian oscillations, supporting optimal immune function and defence against pathogens. Sleep deprivation and disruptions challenge the regulatory mechanisms, making immune responses vulnerable. Altered CR pathways have been implicated in diseases such as diabetes, neurological conditions, and systemic autoimmune diseases (SADs). SADs involve abnormal immune responses to self-antigens, with genetic and environmental factors disrupting self-tolerance and contributing to conditions like Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Inflammatory Myositis. Dysregulated CR may lead to increased production of pro-inflammatory cytokines, contributing to the systemic responses observed in SADs. Sleep disturbances significantly impact the quality of life of patients with SADs; however, they are often overlooked. The relationship between sleep and autoimmune conditions, whether causal or consequential to CR dysregulation, remains unclear. Chrono-immunology investigates the role of CR in immunity, offering potential for targeted therapies in autoimmune conditions. This paper provides an overview of the connections between sleep and autoimmune conditions, highlighting the importance of recognizing sleep disturbances in SADs and the need for further research into the complex relationship between the CR and autoimmune diseases.

The role of circadian clock in regulating cell functions: implications for diseases

“…This association is underscored by a large‐scale population‐based cohort study involving 144,396 patients, which identifies that sleep deprivation markedly increase the susceptibility to SLE 181 . Complementing this finding, additional research suggests that relatives of SLE patients who consistently sleep less than 7 h per night face an elevated risk of developing the disease 182 . Moreover, genetic factors contribute to this correlation as evidenced by the association of single nucleotide polymorphisms in the PER2 gene with both the susceptibility to and clinical manifestations of SLE 183 .…”

“… 181 Complementing this finding, additional research suggests that relatives of SLE patients who consistently sleep less than 7 h per night face an elevated risk of developing the disease. 182 Moreover, genetic factors contribute to this correlation as evidenced by the association of single nucleotide polymorphisms in the PER2 gene with both the susceptibility to and clinical manifestations of SLE. 183 Conversely, patients with SLE, or those at risk of developing it, often experience sleep disturbances, which significantly impair their quality of life.…”

Flight to insight: maximizing the potential of Drosophila models of C9orf72-FTD

“…Disturbances in rhythmicity correlate with disease risk and severity ( Fishbein et al, 2021 ) in a bidirectional manner. This has been validated for numerous pathologies, including immune ( Liu et al, 2017 ; Shivshankar et al, 2020 ; Awuah et al, 2023 ), cardiovascular ( Gottlieb et al, 2019 ; Hayter et al, 2021 ), psychiatric ( Wehr et al, 1987 ; Meyer et al, 2024 ; Scheer and Chellappa, 2024 ), and neurodegenerative disorders ( Fernández-Arcos et al, 2019 ; Sharma et al, 2020 ; Ibrahim et al, 2024 ). Given this wide reach, investigating the circadian dimension of disease is imperative.…”

Circadian Gene Variants in Diseases

“…Circadian proteins influence both innate [ 123 ] and adaptive immunity [ 124 ], as well as the immune response to tumors [ 125 ]. The deregulation of circadian genes has also been shown to play a role in autoimmune diseases [ 126 , 127 ]. However, to the best of our knowledge, there have been no studies observing the associations between specific circadian gene variants and the regulation of immune response.…”