Significance of Interleukin 23 in Systemic Lupus Patients: Relation to Disease Activity and Damage Indices

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Open Access Full Text Article ORIGINAL RESEARCH Significance of Interleukin 23 in Systemic Lupus Patients: Relation to Disease Activity and Damage Indices Maysa M Haroon Wafaa H Hussein 1 , Gehan A Hegazy 2,3 , Mohammed A Hassanien 4,5 , Olfat Shaker 6 , 1 1 Department of Rheumatology, Faculty of Medicine, Cairo University, Cairo, Egypt; 2Clinical Biochemistry Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; 3Medical Division, National Research Centre, Giza, Egypt; 4Vice Presidency for Educational Affairs and Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 5Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta, Egypt; 6Departments of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt Correspondence: Maysa M Haroon, Department of Rheumatology, Faculty of Medicine, Cairo University, 71 El Kasr El Aini Street, P.O.Box 11562, Cairo, Egypt, Tel +201025868370, Email Background: Dysregulation of both cellular and humoral immune responses is central in systemic lupus erythematosus (SLE) pathogenetic mechanisms. Proinflammatory cytokines, such as interleukin 23 (IL23), and their roles in promoting such dysregulation have recently been highly considered. This research compared IL23 serum levels in 85 Egyptian SLE patients and 85 healthy controls. Then, IL23 level was correlated to various SLE disease parameters, disease activity, and damage indices. Results: IL23 serum levels were significantly elevated in SLE patients versus healthy individuals. Furthermore, IL23 levels were positively correlated with SLE disease activity index (SLEDAI) and were positively correlated with arthritis, seizures, consumption of complements (C3, C4), and with parameters of nephritis (hematuria, pyuria, casts, and proteinuria). A positive correlation was also found between IL23 levels and oral prednisolone dose. Conclusion: IL23 has higher levels in the serum of SLE patients, and is correlated to activity of the disease, especially lupus nephritis. Further researchis needed to explore its exact role in SLE pathogenesis and whether it can be considered a potential biomarker or therapeutic target in SLE. Keywords: interleukin 23, proinflammatory cytokines, systemic lupus erythematosus, SLE disease activity index, lupus nephritis The Plain Language Summary Autoimmune diseases occur when your immune system attacks your own body. Systemic lupus erythematosus (SLE) is one of these autoimmune diseases which can affect different tissues, causing great damage. SLE affects more than 5 million people worldwide, mostly women of childbearing age. What makes your immune system behave like this is not fully clear, but it is likely an interaction between your genetics and your environment. The function of your immune system primarily depends on secreted proteins and signal molecules called interleukins (ILs). Some interleukins may be linked to the autoimmune inflammation in SLE, eg, IL23. We compared the amount of IL23 in SLE patients and in normal people. We also checked the link between IL23 and various symptoms of lupus. Interestingly, we found IL23 is higher in SLE patients. Moreover, there was a link between IL23 and serious SLE symptoms. These results are important because they revealed some information about this protein in SLE. We hope that future studies can discover the precise role of IL23 in SLE. In addition, we predict that, in the near future IL23 might be used as a marker for serious SLE symptoms, or a target for new therapy for this challenging disease. Introduction Systemic lupus erythematosus (SLE) is a chronic autoimmune disease distinguished by its very heterogeneous and composite clinical picture. SLE pathogenesis is not completely elucidated but it is believed to be multifactorial, involving hereditary, environmental, as well as hormonal factors. Dysregulation of both cellular and humoral immune responses is Biologics: Targets and Therapy 2023:17 1–9 Received: 7 October 2022 Accepted: 27 December 2022 Published: 18 January 2023 1 © 2023 Haroon et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Dovepress Haroon et al central in SLE pathogenetic mechanisms. The result is disruption of self-tolerance and formation of autoantibodies with subsequent production and precipitation of immune complexes in various organs. This ultimately leads to complement activation and aggregation of neutrophils, monocytes, and lymphocytes.1–3 The role of T-lymphocytes in SLE pathogenesis is evident by signal transduction, aberrant cytokine secretion, in addition to activation and accumulation of B lymphocytes and dendritic cells (DC).4 A subtype of T cells, Th17 is implicated in SLE pathogenesis by producing proinflammatory cytokines, mainly interleukin 17 (IL17), depending on the presence of another cytokine, IL23. IL23 has a role in the growth and differentiation of Th17 as well as its sustained IL17 secretion.5 Interleukin-23 (IL-23) is one of the IL-12 cytokine family. It is a heterodimer that includes IL-12p40 and IL-23p19 subunits. The p19 subunit of IL-23 is formed by antigen-presenting cells (APC) as well as T lymphocytes and endothelial cells. The P40 subunit is formed only by antigen-presenting cells like macrophages, monocytes, and dendritic cells.6,7 Engagement of IL23 to its heterodimeric receptor complex composed of IL-12Rb1 and IL-23R is required to exert its biological activities.7,8 Interleukin-23 was found to be up-regulated in patients with several autoimmune disorders, such as Crohn’s disease, rheumatoid arthritis, and multiple sclerosis.9 Previous studies showed controversial data regarding the association of IL23 with disease activity of SLE through IL17 pathways.5 The current study was conducted to compare the serum levels of IL23 in a cohort of Egyptian SLE patients with those in healthy controls, and to study the correlation of IL23 levels with SLE manifestations, as well as activity and damage indices using the SLE–Disease Activity Index (SLE-DAI) and the Systemic Lupus International Collaborating Clinics/ American College of Rheumatology Damage Index (SLICC/ACR-DI (...truncated)