Serum and Urinary Biomarkers Endothelin-1, Beta-2 Microglobulin, Cystatin C, Galectin-3 and Alpha-1-acid Glycoprotein; Can they Surrogate Clinical and Histological Staging in Lupus Nephritis Patients?

Tony, Effat A.E.; Mohammed, Hanan Sharaf El-Deen; Fathi, Nihal; Tony, Abeer A; Afifi, Ola; Abdou, Madleen A.; Gamal, Rania M.; Saad, Ehab; Fehr, Amal

doi:10.4172/2167-7921.1000223

Cited by 8 publications

(18 citation statements)

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“…Both agents abolished REDD1 upregulation (figure 4C,D, online supplementary figure 4A), resulting in a significant reduction of autophagic levels (figure 4E, online supplementary figure 4B) and subsequent NET formation (figure 4F, online supplementary figure 4C). Importantly, recombinant ET-1 alone in concentration similar to that present in sera from patients with active SLE39 40 neither upregulated REDD1 expression nor induced autophagy and NETs in control neutrophils (online supplementary figure 5A-C). However, combination of recombinant ET-1 with inactive SLE serum upregulated REDD1 expression, enhanced autophagy and led to NET release (online supplementary figure 5A-C) in control neutrophils, similar to stimulation with active SLE serum.…”

Section: Resultsmentioning

confidence: 98%

“…To this end, control neutrophils were pretreated with L-ascorbic acid, a HIF-1α inhibitor or a specific HIF-1α inhibitor (C 26 H 29 NO 5 ) resulting in significant reduction in REDD1 levels (figure 4C,D, online supplementary figure 4A), autophagy induction (figure 4E, online supplementary figure 4B) and subsequent NET release (figure 4F, online supplementary figure 4C). ET-1, a potent vasoconstrictor involved in the mTOR pathway,38 is increased in SLE sera39 40 and correlates with disease activity and LN 41–43. Thus, control neutrophils were treated with the ET-1 receptor antagonist bosentan or a neutralising antibody against ET-1 prior to stimulation with active SLE serum.…”

Section: Resultsmentioning

confidence: 99%

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REDD1/autophagy pathway promotes thromboinflammation and fibrosis in human systemic lupus erythematosus (SLE) through NETs decorated with tissue factor (TF) and interleukin-17A (IL-17A)

et al. 2018

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ObjectivesThe release of neutrophil extracellular traps (NETs) represents a novel neutrophil effector function in systemic lupus erythematosus (SLE) pathogenesis. However, the molecular mechanism underlying NET release and how NETs mediate end-organ injury in SLE remain elusive.MethodsNET formation and NET-related proteins were assessed in the peripheral blood and biopsies from discoid lupus and proliferative nephritis, using immunofluorescence, immunoblotting, quantitative PCR and ELISA. Autophagy was assessed by immunofluorescence and immunoblotting. The functional effects of NETs in vitro were assessed in a primary fibroblast culture.ResultsNeutrophils from patients with active SLE exhibited increased basal autophagy levels leading to enhanced NET release, which was inhibited in vitro by hydroxychloroquine. NETosis in SLE neutrophils correlated with increased expression of the stress-response protein REDD1. Endothelin-1 (ET-1) and hypoxia-inducible factor-1α (HIF-1α) were key mediators of REDD1-driven NETs as demonstrated by their inhibition with bosentan and L-ascorbic acid, respectively. SLE NETs were decorated with tissue factor (TF) and interleukin-17A (IL-17A), which promoted thrombin generation and the fibrotic potential of cultured skin fibroblasts. Notably, TF-bearing and IL-17A-bearing NETs were abundant in discoid skin lesions and in the glomerular and tubulointerstitial compartment of proliferative nephritis biopsy specimens.ConclusionsOur data suggest the involvement of REDD1/autophagy/NET axis in end-organ injury and fibrosis in SLE, a likely candidate for repositioning of existing drugs for SLE therapy. Autophagy-mediated release of TF-bearing and IL-17A-bearing NETs provides a link between thromboinflammation and fibrosis in SLE and may account for the salutary effects of hydroxychloroquine.

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

REDD1/autophagy pathway promotes thromboinflammation and fibrosis in human systemic lupus erythematosus (SLE) through NETs decorated with tissue factor (TF) and interleukin-17A (IL-17A)

et al. 2018

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“…Systemic lupus erythematosus (SLE) is a serologically and clinically heterogeneous illness [1] which leads to malfunction of the immune system [2][3][4][5][6][7][8][9][10][11][12][13]. It is a multiorgan disease stemmed from the production of a broad span of antinuclear antibodies and existence of immune complexes in the involved organs [14]. Moreover, activation of T and B cells in SLE leads to the generation of autoantibodies and damage of tissues [1], evoking loss of self-tolerance.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the serum β2 Microglobulin level in patients with systemic lupus erythematosus and its correlation with disease activity

2019

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Background: Designation of disease activity is serious for the management of systemic lupus erythematosus (SLE). Serum level of β2 microglobulin (β2M) may be associated with illness activity in SLE disease. Since the role of β2M for assessing of illness activity in SLE is not completely clear, the current study aimed to discern evaluation of β2M in patients with SLE and its correlation with sickness activity. Materials and Methods: In this case-control study, 50 patients with SLE disease and 25 healthy individuals were selected in Imam Khomeini Hospital in central of Urmia. Blood samples were collected safely from patients, serum was removed, and β2M measured using an ELISA method. The results for other parameters including C reactive protein, C3, C4, anti dsDNA and erythrocyte sedimentation rate were obtained from patients’ medical record. Data analyzed using appropriate statistical tests including Mann-Whitney U test, Independent f-test, Kruskal-Wallis, and Spearman used for analysis of data. Results: In the current study, a significant difference was seen between two groups in terms of β2M (p < 0.001). Remarkable correlation was seen between the level of β2M with disease activity (p < 0.001). Furthermore, there are significant relevancy between the level of β2M with 24-hour urine protein, ESR, disease activity score, and CRP (p < 0.05). Conclusion: The results revealed that serum amount of β2M in SLE patients is higher compared to healthy ones, which is significantly correlated to score of illness activity, CRP, and ESR in patients with SLE disease. Hence β2M might be an excellent serological marker helping the prediction of sickness activity and inflammation in SLE patients.

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“…Till now, it remains unknown whether KIM-1 could be potentially used as a parameter for the assessment of different kind of injuries in LN [14]. Meanwhile, Endothelin-1 (ET-1) is a 21-amino acid peptide, which is implicated in the development of CKD [17,18]. ET-1 is the most effective endogenous vasoconstrictor as well as being produced within the vasculature and the kidney [19,20].…”

Section: Sampling and Biomarkers Assays For Blood And Urinementioning

confidence: 99%

Urinary VCAM-1, KIM-1, and ET-1 as Biomarkers of Lupus Nephritis: Correlation with Immunological Parameters in Hospital USM

Sm¹,

W²,

M³

et al. 2019

J Rheum Dis Treat

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Introduction: So far, there is no conventional parameters that have been proven to possess the ability to predict the histology of systemic lupus erythematosus (SLE). A few autoimmune serology markers of SLE including anti-dsDNA antibodies, complement C3 and C4, and anti-nucleosome could be helpful clinically, but the correlation between those and lupus renal disease is still imperfect. Recently, the urinary vascular cell adhesion molecule-1 (VCAM-1), kidney injury molecule-1 (KIM-1) and endothelin-1 (ET-1) have been studied for the diagnosis of lupus nephritis (LN). Nevertheless, it is still unknown whether the urinary VCAM-1, KIM-1 and ET-1 could be used as disease monitoring and flare predictor tools for LN.Objective: To evaluate the levels of VCAM-1, KIM-1, and ET-1 in active LN, inactive LN and controls, cut-off points and diagnostic accuracy and their correlation with SLE Disease Activity Index (SLEDAI), renal SLEDAI (rSLEDAI), and the standard immunological markers.Methods: This study involved 60 LN patients and 30 controls conducted in the Hospital Universiti Sains Malaysia (Hospital USM) from September 2016 to February 2018. All three biomarkers were determined by enzyme-linked immunosorbent assay (ELISA) in urine samples of patients. Receiver operating characteristic analysis was performed to obtain the best cut-off values and to calculate the performance of these markers. The correlation was done between urinary biomarkers and immunological parameters. Statistical analysis was performed using SPSS software, version 22.0.Results: Urinary VCAM-1, KIM-1, and ET-1 levels were significantly higher in active LN patients compared to inactive LN patients and controls. These markers correlated significantly with anti-dsDNA, complement C3, complement C4, urine protein/urine creatinine (Uprot/Ucreat), SLE disease activity index (SLEDAI), and renal SLEDAI scores. The urinary KIM-1 significantly correlated with all the immunological parameters except for complement C4. Urinary ET-1 showed higher specificity and sensitivity in differentiating LN patients and healthy controls (AUC 0.809) than urinary VCAM-1 (AUC 0.725) and urinary KIM-1 (AUC 0.640). Conclusions:Our study demonstrated that urinary VCAM-1, KIM-1, and ET-1 might be potential biomarkers specific for the lupus renal disease.

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Serum and Urinary Biomarkers Endothelin-1, Beta-2 Microglobulin, Cystatin C, Galectin-3 and Alpha-1-acid Glycoprotein; Can they Surrogate Clinical and Histological Staging in Lupus Nephritis Patients?

Cited by 8 publications

References 0 publications

REDD1/autophagy pathway promotes thromboinflammation and fibrosis in human systemic lupus erythematosus (SLE) through NETs decorated with tissue factor (TF) and interleukin-17A (IL-17A)

REDD1/autophagy pathway promotes thromboinflammation and fibrosis in human systemic lupus erythematosus (SLE) through NETs decorated with tissue factor (TF) and interleukin-17A (IL-17A)

Evaluation of the serum β2 Microglobulin level in patients with systemic lupus erythematosus and its correlation with disease activity

Urinary VCAM-1, KIM-1, and ET-1 as Biomarkers of Lupus Nephritis: Correlation with Immunological Parameters in Hospital USM

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