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

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          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.

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          To characterize the role of the circadian clock in mouse physiology and behavior, we used RNA-seq and DNA arrays to quantify the transcriptomes of 12 mouse organs over time. We found 43% of all protein coding genes showed circadian rhythms in transcription somewhere in the body, largely in an organ-specific manner. In most organs, we noticed the expression of many oscillating genes peaked during transcriptional "rush hours" preceding dawn and dusk. Looking at the genomic landscape of rhythmic genes, we saw that they clustered together, were longer, and had more spliceforms than nonoscillating genes. Systems-level analysis revealed intricate rhythmic orchestration of gene pathways throughout the body. We also found oscillations in the expression of more than 1,000 known and novel noncoding RNAs (ncRNAs). Supporting their potential role in mediating clock function, ncRNAs conserved between mouse and human showed rhythmic expression in similar proportions as protein coding genes. Importantly, we also found that the majority of best-selling drugs and World Health Organization essential medicines directly target the products of rhythmic genes. Many of these drugs have short half-lives and may benefit from timed dosage. In sum, this study highlights critical, systemic, and surprising roles of the mammalian circadian clock and provides a blueprint for advancement in chronotherapy.
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            2019 update of the EULAR recommendations for the management of systemic lupus erythematosus

            Our objective was to update the EULAR recommendations for the management of systemic lupus erythematosus (SLE), based on emerging new evidence. We performed a systematic literature review (01/2007–12/2017), followed by modified Delphi method, to form questions, elicit expert opinions and reach consensus. Treatment in SLE aims at remission or low disease activity and prevention of flares. Hydroxychloroquine is recommended in all patients with lupus, at a dose not exceeding 5 mg/kg real body weight. During chronic maintenance treatment, glucocorticoids (GC) should be minimised to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn. Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of GC. In persistently active or flaring extrarenal disease, add-on belimumab should be considered; rituximab (RTX) may be considered in organ-threatening, refractory disease. Updated specific recommendations are also provided for cutaneous, neuropsychiatric, haematological and renal disease. Patients with SLE should be assessed for their antiphospholipid antibody status, infectious and cardiovascular diseases risk profile and preventative strategies be tailored accordingly. The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion.
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                Author and article information

                Contributors
                Journal
                Medicine (Baltimore)
                MD
                Medicine
                Lippincott Williams & Wilkins (Hagerstown, MD )
                0025-7974
                1536-5964
                11 August 2023
                11 August 2023
                : 102
                : 32
                : e34614
                Affiliations
                [a ] Faculty of Medicine, Sumy State University, Sumy, Ukraine
                [b ] Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland
                [c ] Drexel University College of Medicine, Philadelphia, PA
                [d ] University of Debrecen-Faculty of Medicine, Debrecen, Hungary
                [e ] SUNY Upstate Medical University, Syracuse, NY
                [f ] Faculty of Medicine and Health Sciences, University of Putra Malaysia, Serdang, Malaysia
                [g ] Faculty of Medicine, University of St Andrews, Scotland, UK
                [h ] School of Clinical Medicine, University of Cambridge, Cambridge, UK
                [i ] School of Medicine, Queen’s University Belfast, Belfast, UK
                [j ] Institute of Medical Sciences and SUM Hospital, Bhubaneswar, India
                [k ] Rowan University School of Osteopathic Medicine, Stratford, NJ
                [l ] Department of Microbiology, West Bengal State University, Barasat, India
                [m ] Department of Health Sciences, Novel Global Community Educational Foundation, Hebersham, NSW
                [n ] Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, NSW
                [o ] Department of Surgery II, University Hospital Witten-Herdecke, Heusnerstrasse 40, University of Witten-Herdecke, Wuppertal, Germany.
                Author notes
                [* ]Correspondence: Favour Tope Adebusoye, Sumy State University, Zamonstanksya 7, Sumy 40007, Ukraine (e-mail: favouradebusoye@ 123456gmail.com ).
                Author information
                https://orcid.org/0000-0001-5362-3920
                Article
                00081
                10.1097/MD.0000000000034614
                10419593
                37565922
                d245291d-a399-464b-9cc3-eda81d90d018
                Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 06 June 2023
                : 13 July 2023
                : 14 July 2023
                Categories
                3600
                Research Article
                Narrative Review
                Custom metadata
                TRUE

                chrono-immunology,circadian rhythm,systemic autoimmune diseases

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