The role of cytokines as biomarkers in systemic lupus erythematosus and lupus nephritis

Cytotoxic CD8+ T-cells play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study was to investigate the role of CD107a (LAMP-1) on cytotoxic CD8+ T-cells in SLE-patients in particular with lupus nephritis. Peripheral blood of SLE-patients (n = 31) and healthy controls (n = 21) was analyzed for the expression of CD314 and CD107a by flow cytometry. Kidney biopsies of lupus nephritis patients were investigated for the presence of CD8+ and C107a+ cells by immunohistochemistry and immunofluorescence staining. The percentages of CD107a+ on CD8+ T-cells were significantly decreased in SLE-patients as compared to healthy controls (40.2 ± 18.5% vs. 47.9 ± 15.0%, p = 0.02). This was even more significant in SLE-patients with inactive disease. There was a significant correlation between the percentages of CD107a+CD8+ T-cells and SLEDAI. The evaluation of lupus nephritis biopsies showed a significant number of CD107a+CD8+ T-cells mainly located in the peritubular infiltrates. The intrarenal expression of CD107a+ was significantly correlated with proteinuria. These results demonstrate that CD8+ T-cells of patients with systemic lupus erythematosus have an altered expression of CD107a which seems to be associated with disease activity. The proof of intrarenal CD107a+CD8+ suggests a role in the pathogenesis of lupus nephritis.

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Role of the Fc? receptor IIa polymorphism in susceptibility to systemic lupus erythematosus and lupus nephritis: A meta-analysis

Arthritis & Rheumatism ◽

10.1002/art.10306 ◽

2002 ◽

Vol 46 (6) ◽

pp. 1563-1571 ◽

Cited By ~ 155

Author(s):

Fotini B. Karassa ◽

Thomas A. Trikalinos ◽

John P. A. Ioannidis ◽

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Nephritis ◽

Lupus Erythematosus ◽

Meta Analysis ◽

Fc Receptor ◽

Systemic Lupus

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POS0788 CIRCULATING EXOSOMES PROMOTE LUPUS NEPHRITIS IN MRL-LPR MICE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3904 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 646.3-647

Author(s):

X. Sha ◽

X. Ge ◽

Y. Jin ◽

T. Chen ◽

X. Ni ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Nephritis ◽

Western Blot ◽

Lupus Erythematosus ◽

Expression Profiles ◽

Meta Analysis ◽

Differentially Expressed ◽

Systemic Lupus ◽

Exosomal Mirnas

Background:Systemic Lupus Erythematosus (SLE) is a prototypic autoimmune disease that characterized by the loss of self-tolerance and the production of autoantibodies (autoAbs) [1, 2]. Lupus nephritis (LN), the severe organ-threatening manifestations of SLE, could cause massive damage to patients[3, 4]. Currently, some exosomal microRNAs (miRNAs) are considered as potential biomarkers in SLE. However, the role of exosomal miRNAs in Lupus Nephritis (LN) remains unclear.Objectives:The purpose of this study was to investigate molecular mechanism of plasma exosomal miRNAs in the development of Lupus Nephritis.Methods:Circulating exosomes were isolated from plasma of patients with LN, SLE without LN (NLN). Plasma exosomes were authenticated by Western Blot, Nanosight Tracking Analysis (NTA) and transmission electron microscopy (TEM). Fluorescence microscopy of co-cultured plasma exosomes and podocytes demonstrated that exosomes were uptaken into podocytes. Moreover, cell apoptosis and the inflammation factors was assessed using Western Blot. We analyzed the expression profiles of miRNAs in LN and NLN exosomes and the expression profiles of mRNAs of podocytes stimulated with LN and NLN exosomes with the help of next generation sequencing (NGS).Results:We demonstrate that exosomes derived from LN plasma could be taken by neighboring podocytes and promote the apoptosis of podocytes and the expression of inflammation factors. In addition, the sequencing found that miRNAs were differentially expressed in LN and NLN exosomes and mRNAs were differentially expressed in podocytes stimulated with LN and NLN exosomes.Conclusion:LN plasma exosomes have a potency to stimulate the apoptosis of podocytes and the expression of inflammation factors. Moreover, differentially expressed miRNAs in exosomes play a potential role in the development of LN.References:[1]T. Colasanti, A. Maselli, F. Conti, M. Sanchez, C. Alessandri, C. Barbati, D. Vacirca, A. Tinari, F. Chiarotti, A. Giovannetti, F. Franconi, G. Valesini, W. Malorni, M. Pierdominici, E. Ortona, Autoantibodies to estrogen receptor α interfere with T lymphocyte homeostasis and are associated with disease activity in systemic lupus erythematosus, Arthritis and rheumatism, 64 (2012) 778-787.[2]H.A. Al-Shobaili, A.A. Al Robaee, A.A. Alzolibani, Z. Rasheed, Antibodies against 4-hydroxy-2-nonenal modified epitopes recognized chromatin and its oxidized forms: role of chromatin, oxidized forms of chromatin and 4-hydroxy-2-nonenal modified epitopes in the etiopathogenesis of SLE, Disease markers, 33 (2012) 19-34.[3]A. Kaul, C. Gordon, M.K. Crow, Z. Touma, M.B. Urowitz, R. van Vollenhoven, G. Ruiz-Irastorza, G. Hughes, Systemic lupus erythematosus, Nat Rev Dis Primers, 2 (2016) 16039.[4]M.G. Tektonidou, A. Dasgupta, M.M. Ward, Risk of End-Stage Renal Disease in Patients With Lupus Nephritis, 1971-2015: A Systematic Review and Bayesian Meta-Analysis, Arthritis & rheumatology (Hoboken, N.J.), 68 (2016) 1432-1441.Disclosure of Interests:None declared

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Emerging Role of Circular RNAs in Kidney Diseases in Nephrology

Current Drug Targets ◽

10.2174/1389450122666210806124425 ◽

2021 ◽

Vol 22 ◽

Author(s):

Cong Ma ◽

Junjun Luan ◽

Jeffrey B. Kopp ◽

Hua Zhou

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Nephritis ◽

Lupus Erythematosus ◽

Kidney Diseases ◽

Kidney Tissue ◽

Current Status ◽

Renal Diseases ◽

Circular Rnas ◽

Systemic Lupus

Background: Circular RNAs (circRNAs) have been identified to be involved in a variety of human diseases such as cancers, cardiovascular diseases, and autoimmune diseases. In recent years, the role of circRNAs in the development of kidney diseases in nephrology has been gradually recognized. Objective: We updated and described the current status of circRNAs in kidney diseases in nephrology. We particularly focused on the roles and mechanisms of circRNAs in systemic lupus erythematosus and lupus nephritis. Methods: We summarized recent reports published on PubMed, Web of Science, Scopus, Scielo databases using key words circRNAs, kidney diseases or renal diseases, or systemic lupus erythematosus. Results: Studies of circRNAs in certain kidney diseases such as acute kidney injury, focal segmental glomerulosclerosis, idiopathic membranous nephropathy, IgA nephropathy, diabetic nephropathy, hypertensive renal damage and particular lupus nephritis address the function and pathogenesis of circRNAs in these diseases. Mechanisms of circRNAs in the above human kidney diseases so far have focused on the role of sponging microRNAs and regulating the expression of target genes. Moreover, circRNAs have been detected in blood, urine, and kidney tissue samples. These results suggest that circRNAs can serve as biomarkers for the diagnosis and monitoring the progression of kidney diseases. Conclusion: CircRNAs play important roles in the pathogenesis, diagnosis, and treatment of kidney diseases emphasizing lupus nephritis in nephrology.

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The role of Dickkopf-1 as a biomarker in systemic lupus erythematosus and active lupus nephritis

Egyptian Rheumatology and Rehabilitation ◽

10.1186/s43166-021-00064-3 ◽

2021 ◽

Vol 48 (1) ◽

Author(s):

Mervat E. Abdelazeem ◽

Marwa I. Abdelhaleem ◽

Rabab A. Mohamed ◽

Enas A. Abdelaleem

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Nephritis ◽

Disease Activity ◽

Lupus Erythematosus ◽

Serum Levels ◽

Renal Diseases ◽

Systemic Lupus ◽

Active Lupus Nephritis ◽

Active Lupus

Abstract Background Systemic lupus erythematosus (SLE) is a chronic disease which is mainly attributed to autoantibodies, cytokines, and immune complex deposition. Studies have demonstrated that cytokines and autoantibodies were strongly associated with renal diseases and can be used for the prediction of patients with lupus nephritis (LN). However, antibodies to dsDNA and the reduction of complements were also detected in non-LN patients as well as clinically non-active SLE patients. The current study was performed to detect the role of serum DKK-1 as a biomarker for the identification of SLE patients and patients with LN and its relation to disease activity and severity. The study was conducted on fifty clinically diagnosed SLE patients who were diagnosed according to Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE, in addition to thirty healthy control volunteers matched for age and sex. Assessment of SLE disease activity was done using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Assessment of SLE disease severity was done using the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index. Serum levels of DKK-1 were measured for all participants by ELISA using commercially available kits. Results DKK-1 serum levels were significantly higher among active lupus nephritis cases as compared with SLE cases with no LN and with healthy controls (9197.60 μg/uL ± 2939.2 μg/uL vs. 6405.15 μg/uL ± 2018.91 μg/uL vs. 2790.33 μg/uL ± 833.49 μg/uL) respectively (p-values < 0.001). DKK-1 concentration was significantly higher among SLE patients with positive as compared with negative anti-double-stranded DNA (dsDNA) antibodies (p-value < 0.001). According to receiver operating characteristic (ROC) curve analysis, serum DKK-1 level diagnosed the SLE at a statistically significant level with a 98% sensitivity and 70% specificity and serum DKK-1 level also diagnosed active lupus nephritis at a 90% sensitivity and 63% specificity. Conclusion DKK-1 could diagnose SLE and lupus nephritis with high sensitivity and specificity. Serum DKK-1 is a reliable biomarker for the identification of SLE and patients with LN and could be used as a key molecule for the diagnosis of SLE and as a prognostic indicator of LN.

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