scholarly journals Soluble Fas and the −670 Polymorphism of Fas in Lupus Nephritis

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Juan José Bollain-y-Goytia ◽  
Mariela Arellano-Rodríguez ◽  
Felipe de Jesús Torres-Del-Muro ◽  
Leonel Daza-Benítez ◽  
José Francisco Muñoz-Valle ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Healthy Subjects ◽  
Rflp Analysis ◽  
Allelic Frequency ◽  
Soluble Fas ◽  
Pcr Rflp ◽  
Sfas Level

This study was performed to clarify the role of soluble Fas (sFas) in lupus nephritis (LN) and establish a potential relationship between LN and the −670 polymorphism of Fas in 67 patients with systemic lupus erythematosus (SLE), including a subset of 24 LN patients with proteinuria. Additionally, a group of 54 healthy subjects (HS) was included. The allelic frequency of the −670 polymorphism of Fas was determined using PCR-RFLP analysis, and sFas levels were assessed by ELISA. Additionally, the WT-1 protein level in urine was measured. The Fas receptor was determined in biopsies by immunohistochemistry (IHC) andin situhybridization (FISH) and apoptotic features by TUNEL.Results. The −670 Fas polymorphism showed that the G allele was associated with increased SLE susceptibility, with an odds ratio (OR) of 1.86. The sFas was significantly higher in LN patients with the G/G genotype, and this subgroup exhibited correlations between the sFas level and proteinuria and increased urinary WT-1 levels. LN group shows increased expression of Fas and apoptotic features. In conclusion, our results indicate that the G allele of the −670 polymorphism of Fas is associated with genetic susceptibility in SLE patients with elevated levels of sFas in LN with proteinuria.

scholarly journals T cell–specific STAT3 deficiency abrogates lupus nephritis

Lupus ◽  
2019 ◽  
Vol 28 (12) ◽  
pp. 1468-1472 ◽  
Author(s):  
N Yoshida ◽  
F He ◽  
V C Kyttaris
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Cell Responses ◽  
Cytokines And Chemokines ◽  
Novel Approach ◽  
Cell Tissue ◽  
External Stimuli

Signal transducer and activator of transcription (STAT) 3 is a regulator of T-cell responses to external stimuli, such as pro-inflammatory cytokines and chemokines. We have previously shown that STAT3 is activated (phosphorylated) at high levels in systemic lupus erythematosus (SLE) T cells and mediates chemokine-induced migration and T:B cell interactions. Stattic, a small molecular STAT3 inhibitor, can partially ameliorate lupus nephritis in mice. To understand the role of STAT3 better in T-cell pathophysiology in lupus nephritis and its potential as a treatment target, we silenced its expression in T cells using a cd4-driven CRE-Flox model. We found that lupus-prone mice that do not express STAT3 in T cells did not develop lymphadenopathy, splenomegaly, or glomerulonephritis. Moreover, the production of anti-dsDNA antibodies was decreased in these mice compared to controls. To dissect the mechanism, we also used a nephrotoxic serum model of nephritis. In this model, T cell–specific silencing of STAT3 resulted in amelioration of nephrotoxic serum-induced kidney damage. Taken together, our results suggest that in mouse models of autoimmune nephritis, T cell–specific silencing of STAT3 can hamper their ability to help B cells to produce autoantibodies and induce cell tissue infiltration. We propose that STAT3 inhibition in T cells represents a novel approach in the treatment of SLE and lupus nephritis in particular.

Predictive value of the neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-neutrophil ratio, and neutrophil-to-monocyte ratio in lupus nephritis

Lupus ◽  
2020 ◽  
Vol 29 (9) ◽  
pp. 1031-1039
Author(s):  
Peng Liu ◽  
Peiyuan Li ◽  
Zhong Peng ◽  
Yazhou Xiang ◽  
Chenqi Xia ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Healthy Subjects ◽  
Area Under The Curve ◽  
Neutrophil To Lymphocyte Ratio ◽  
Control Group ◽  
Receiver Operating Characteristic Curves ◽  
Lymphocyte Ratio ◽  
And Control ◽  
First Time

Objective To evaluate the role of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-neutrophil ratio (PNR), platelet-to-monocyte ratio (PMR), and neutrophil-to-monocyte ratio (NMR) as predictors for lupus nephritis (LN) patients without infection or as biomarkers for distinguishing between infection or flare with LN patients. Methods LN patients were divided into three groups: LN without infection, LN with infection, and LN with flare. A total of 57 healthy subjects were enrolled as controls. The differentiation was analyzed between LN without infection and control group, and LN with infection and LN with flare. Correlations among variables were assessed in the LN group without infection. Receiver operating characteristic curves were constructed in two comparable groups. Results NLR, PLR, and MLR were increased significantly in the LN group without infection as compared with those in healthy controls. NLR (area under the curve (AUC): 0.75) and MLR (AUC: 0.79) were useful for distinguishing between LN patients without infection and healthy subjects. In differentiating LN patients without infection from the controls, optimal cutoffs of NLR and MLR were 3.43 (sensitivity: 45.6%, specificity: 96.5%, and overall accuracy: 68.8%) and 0.24 (sensitivity: 75.0%, specificity: 73.7%, and overall accuracy: 73.6%), respectively. In addition, NLR ( r = 0.322, p = 0.011) and PLR ( r = 0.283, p = 0.026) were positively correlated with CRP. Importantly, NLR and NMR were increased while PNR was decreased in the LN group with infection in comparison with those in the LN group with flare. NLR (AUC: 0.80), NMR (AUC: 0.78), and PNR (AUC: 0.74) were useful in differentiating LN patients with infection and flare, and their optimal cutoffs were 4.02 (sensitivity: 82.6%, specificity: 69.6%, and overall accuracy: 75.5%), 12.19 (sensitivity: 80.4%, specificity: 73.9%, and overall accuracy: 77.5%), and 28.26 (sensitivity: 65.2%, specificity: 76.8%, and overall accuracy: 71.6%), respectively. Conclusions We demonstrated, for the first time, that MLR or NMR had the best accuracy in differentiating LN patients without infection from healthy subjects, or differentiating infection from flare in LN patients, respectively. Our results implied that NLR, MLR, PNR, and NMR may be useful biomarkers in predicting LN.

scholarly journals Malarial Infection of Female BWF1 Lupus Mice Alters the Redox State in Kidney and Liver Tissues and Confers Protection against Lupus Nephritis

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Saleh Al-Quraishy ◽  
Mostafa A. Abdel-Maksoud ◽  
Azza El-Amir ◽  
Fathy A. Abdel-Ghaffar ◽  
Gamal Badr
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Redox State ◽  
Ultrastructural Changes ◽  
Liver And Kidney ◽  
Gamma Irradiated ◽  
Kidney Functions ◽  
Tropical Infections ◽  
Liver Tissues

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by an imbalanced redox state and increased apoptosis. Tropical infections, particularly malaria, may confer protection against SLE. Oxidative stress is a hallmark of SLE. We have measured changes in the levels of nitric oxide (NO), hydrogen peroxide (H2O2), malondialdehyde (MDA), and reduced glutathione (GSH) in both kidney and liver tissues of female BWF1 lupus mice, an experimental model of SLE, after infection with either live or gamma-irradiated malaria. We observed a decrease in NO, H2O2, and MDA levels in kidney tissues after infection of lupus mice with live malaria. Similarly, the levels of NO and H2O2were significantly decreased in the liver tissues of lupus mice after infection with live malaria. Conversely, GSH levels were obviously increased in both kidney and liver tissues after infection of lupus mice with either live or gamma-irradiated malaria. Liver and kidney functions were significantly altered after infection of lupus mice with live malaria. We further investigated the ultrastructural changes and detected the number of apoptotic cells in kidney and liver tissues in situ by electron microscopy and TUNEL assays. Our data reveal that infection of lupus mice with malaria confers protection against lupus nephritis.

scholarly journals THE PREVALENCE OF PAI-1 4G/5G POLYMORPHISM IN WOMEN WITH FETAL LOSS – FIRST DATA FOR A SERBIAN POPULATION / UČESTALOST POLIMORFIZMA PAI-1 4G/5G KOD ŽENA SA SPONTANIM POBAČAJEM - PRVI PODACI ZA SRPSKU POPULACIJU

2013 ◽  
Vol 33 (2) ◽  
pp. 203-207 ◽  
Author(s):  
Valentina Đorđević ◽  
Maja Gvozdenov ◽  
Iva Pruner ◽  
Mirjana Kovač ◽  
Branko Tomić ◽  
...  
Keyword(s):  
Fetal Loss ◽  
Rflp Analysis ◽  
Plasminogen Activator Inhibitor ◽  
Second Trimester ◽  
Plasminogen Activator Inhibitor 1 ◽  
Over Expression ◽  
Increased Risk ◽  
Pcr Rflp ◽  
Pai 1

Summary Background: Plasminogen activator inhibitor 1 (PAI-1) is an inhibitor of fibrinolysis. The PAI-1 4G/5G polymorphism is associated with elevated plasma levels of PAI-1. Over- expression of PAI-1 and impaired fibrinolysis in homozygous carriers of the 4G/4G PAI polymorphism may lead to abnor- mal placental formation and increased risk of fetal loss (FL). The aim of our study was to determine the frequency of this polymorphism in patients with FL in a Serbian population. Methods: The study was carried out in a group of 203 women (91 controls and 112 women with FL). The presence of PAI-1 4G/5G polymorphism was detected by PCR-RFLP analysis. Results: Slightly increased frequency of the PAI-1 4G/4G genotype was observed in the study group compared to the controls (32.1% vs. 30.8%). The frequency of PAI-1 was highest in women experiencing FL in the second trimester of pregnancy (50%), but this difference was not statistically sig- nificant. Conclusions: Our findings suggest that PAI-1 4G/4G might be a risk factor for FL occurring in the second trimester of pregnancy. Further studies are required in order to determine the role of PAI-1 4G/5G polymorphism in the etiology of FL.

scholarly journals Role of the Specialized Proresolving Mediator Resolvin D1 in Systemic Lupus Erythematosus: Preliminary Results

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Luca Navarini ◽  
Tiziana Bisogno ◽  
Domenico Paolo Emanuele Margiotta ◽  
Alessandra Piccoli ◽  
Silvia Angeletti ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Roc Curve ◽  
Lupus Erythematosus ◽  
Plasma Levels ◽  
Healthy Subjects ◽  
Systemic Disease ◽  
University Hospital ◽  
Resolvin D1 ◽  
Systemic Lupus

Objective. Systemic lupus erythematosus (SLE) is an autoimmune systemic disease and its pathogenesis has not yet been completely clarified. Patients with SLE show a deranged lipid metabolism, which can contribute to the immunopathogenesis of the disease and to the accelerated atherosclerosis. Resolvin D1 (RvD1), a product of the metabolism of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA), acts as a specialized proresolving mediator which can contribute in restoring the homeostasis in inflamed tissues. The aim of the present pilot study is to evaluate plasma levels of RvD1 in patients with SLE and healthy subjects, investigating its potential role as a biomarker of SLE and assessing its relationship with disease activity and laboratory parameters. Methods. Thirty patients with SLE and thirty age- and sex-matched healthy subjects (HSs) have been consecutively recruited at Campus Bio-Medico University Hospital. RvD1 plasma levels were measured by ELISA according to the manufacturer’s protocol (Cayman Chemical Co.). RvD1 levels were compared using Mann–Whitney test. Discriminatory ability for SLE has been evaluated by the area under the ROC curve. Results. Lower levels of RvD1, 45.6 (35.5–57.4) pg/ml, in patients with SLE have been found compared to HSs, 65.1 (39.43–87.95) pg/ml (p=0.0043). The area under the ROC curve (AUC) for RvD1 was 0.71 (95% CI: 0.578–0.82) and the threshold value of RvD1 for the classification of SLE was <58.4 pg/ml, sensitivity 80% (95% CI: 61.4–92.3), and specificity 63.3% (95% CI: 43.9–80.1), likelihood ratio 2.2 (95% CI: 1.3–3.6). Conclusions. The present preliminary study allows hypothesizing a dysregulation of RvD1 in patients with SLE, confirming the emerging role of bioactive lipids in this disease.

Role of micro-RNA132 and its long non coding SOX2 in diagnosis of lupus nephritis

Lupus ◽  
2022 ◽  
pp. 096120332110671
Author(s):  
Rasha F Ahmed ◽  
Olfat Gamil Shaker ◽  
Hend M abdelghany ◽  
Nilly Helmy Abdallah ◽  
Samar Hisham Elsayed ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Molecular Mechanisms ◽  
Activity Index ◽  
Disease Activity Index ◽  
Clinical Indicators ◽  
Sox2 Expression ◽  
Micro Rnas ◽  
Patient Groups

Background The skin and the kidney are commonly affected in systemic lupus erythematosus (SLE) with similar molecular mechanisms. Although clinical indicators of renal injury in SLE are fairly uncontroversial, few biomarkers are reliable. The role of micro-RNAs (mi-RNAs) in lupus nephritis (LN) pathogenesis has been investigated to help in early diagnosis. Purpose The aim of work is to evaluate miRNA132 and SOX2 expressions in SLE Egyptian patients; with and without nephritis, and the relation between miRNA132 and its long non-coding gene SOX2 in both patients groups. Research Design This is a case-control study involving 100 SLE patients with and without LN (LN and non-LN groups), and 50 age-and sex-matched healthy controls. The study was carried out to detect miRNA132 and SOX2 expression by quantitative Real-Time Polymerase chain reaction methods. The SLE disease activity index (SLEDAI) was assessed. Results SLEDAI increased in LN compared to non-LN. Micro-RNA132 expression was significantly increased in patient groups compared to controls ( p<0.01) and increased in LN more than non-LN group ( p<0.001). SOX2 significantly decreased in patient groups compared to controls ( p<0.001), and was more in LN compared to non-LN group ( p<0.001). There was a negative correlation between miRNA132 and SOX2 expression in both patient groups ( p<0.001). Conclusion miRNA132 and SOX2 may play a role in SLE activity and help in the early non-invasive diagnosis of LN.

scholarly journals The Role of Hyaluronan and CD44 in the Pathogenesis of Lupus Nephritis

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Susan Yung ◽  
Tak Mao Chan
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Cell Surface Receptor ◽  
Systemic Lupus ◽  
Permanent Damage ◽  
Immune Mediated ◽  
Surface Receptor

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease that affects multiorgan systems. Lupus nephritis is one of the most severe manifestations of SLE whereby immune-mediated inflammation can lead to permanent damage within the glomerular, tubulo-interstitial, and vascular compartments of the kidney, resulting in acute or chronic renal failure. The mechanisms that regulate host inflammatory responses and tissue injury are incompletely understood. Accumulating evidence suggests that hyaluronan and its interaction with its cell surface receptor CD44 plays an important role in mediating pathogenic mechanisms in SLE. This paper discusses the putative mechanisms through which hyaluronan and CD44 contribute to the pathogenesis of SLE, with particular emphasis on lupus nephritis.

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