The behavior of neutrophil extracellular traps and NADPH oxidative activity in pediatric systemic lupus erythematosus: relation to disease activity and lupus nephritis

2019 ◽  
Vol 38 (9) ◽  
pp. 2585-2593 ◽  
Author(s):  
Dalia Helmy El-Ghoneimy ◽  
Mohamed Hesham ◽  
Rasha Hasan ◽  
Mohamed Tarif ◽  
Sally Gouda
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Neutrophil Extracellular Traps ◽  
Oxidative Activity ◽  
Systemic Lupus ◽  
Pediatric Systemic Lupus Erythematosus ◽  
Extracellular Traps

scholarly journals Degradation of neutrophil extracellular traps co-varies with disease activity in patients with systemic lupus erythematosus

2013 ◽  
Vol 15 (4) ◽  
pp. R84 ◽  
Author(s):  
Jonatan Leffler ◽  
Birgitta Gullstrand ◽  
Andreas Jönsen ◽  
Jan-Åke Nilsson ◽  
Myriam Martin ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Neutrophil Extracellular Traps ◽  
Systemic Lupus ◽  
Extracellular Traps

O004. Assessment of the impact of lupus nephritis on clinical, biological parameters, disease activity and mortality in pediatric Systemic Lupus Erythematosus

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_5) ◽  
Author(s):  
O Gacem ◽  
L Labboun ◽  
N Ayad ◽  
Z Zeroual ◽  
Z Arrada ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Renal Failure ◽  
Chronic Renal Failure ◽  
Lupus Nephritis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Systemic Lupus Erythematosus Disease ◽  
Systemic Lupus ◽  
Pediatric Systemic Lupus Erythematosus ◽  
The Impact

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple organ systems. Kidney involvement is one of the most frequent and severe manifestations of pediatric systemic lupus erythematosus (pSLE), seriously affecting the prognosis. It usually manifests as glomerulonephritis of varying severity. Objective: Knowledge of the correlation of lupus nephritis (LN) with clinical, biological, immunological parameters, disease activity and mortality in pediatric systemic lupus erythematosus is limited. This study aims to describe the impact of renal involvement with these different determinants. Methods This was a prospective, multicenter, descriptive 36-month study (January 2015 - December 2018) including patients less than 16 years of age with LN. The presence of LN was defined according to the American College of Rheumatology classification SLE criteria. The LN class was determined by renal biopsy and was classified according to the Morphology in Kidney International Society of Nephrology (ISN)/Renal Pathology Society (RPS) 2004 classification of lupus nephritis. The disease activity was estimated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the use of which has been validated in children. Means, percentages and Chi-square tests were specified. P values less than 0.05 were considered statistically significant. Results We included 83 patients in this study. 37/83 patients (44.6%) developed LN with the following urinary signs: 92% of proteinuria (mean 3366.147 mg ± 2785.93 / 24h) including 2/3 of cases of nephrotic syndrome, 81% of hematuria, 14% of acute renal failure with significant reduction in glomerular filtration rate (average creatinine clearance of 32.42 ml / min) and 12% high blood pressure. Out of a total of 30 renal biopsies interpreted at disease diagnosis, 73.4% diffuse proliferative glomerulonephritis forms were observed: (III (30%), IV (36.7%) and VI (6, 7%)). Lupus nephritis were significantly correlated with hypocomplementemia in its C3 (P = 0.00002) and C4 (P = 0.00005) fraction, lymphopenia (P = 0.02), anti-DNA antibodies (P = 0.026), SLEDAI (P = 0.00001) and mortality (P = 0.03). The most frequently used induction drugs for LN classes III, IV and VI were pulsed intravenous methylprednisolone (500 mg daily for 3 doses) in combination with low dose intravenous cyclophosphamide (23%) in the short term (500 mg/m2/15 days X 6) followed by mycophenolate mofetil (28%) (600mg/ m2 in two daily doses) as maintenance treatment associated with a daily dose of oral glucocorticoids with a gradual decrease until reaching the minimum amount necessary to control the disease. All of our SLE patients with nephritis were treated with HCQ with a significant correlation with the decrease in SLEDAI. During the first two years of disease progression, the frequency of LN increased to 43/83 (51.8%) mainly in these severe forms: (IV (41.7%), V (2.8 %). The progression to chronic renal failure had a prevalence of 6, 9% (3/43) of cases; these were mainly patients with severe lupus nephritis (III, and IV) Conclusion Nephritis is a major risk factor for morbidity and mortality in pSLE; LN in children is most often proliferating and more active. The early diagnosis and management of kidney damage are the only guarantee of a good course and prevention of the progression of chronic renal failure. Keywords lupus nephritis; child; systemic lupus erythematosus; disease activity, mortality.

scholarly journals Assessment of SLEDAI Score in Children with Lupus Nephritis Class III-IV in Vietnam National Children’s Hospital

2020 ◽  
Vol 36 (2) ◽  
Author(s):  
Duong Thi Thanh Binh ◽  
Nguyen Thu Huong ◽  
Nguyen Thi Kien ◽  
Pham Van Dem ◽  
Tran Minh Dien
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Disease Activity Index ◽  
Class Iii ◽  
Systemic Lupus ◽  
Sledai Score ◽  
Pediatric Systemic Lupus Erythematosus

This study describes clinical, paraclinical characteristics and treatment response in children with nephritis class II-IV caused by systemic lupus erythematosus and validates SLEDAI for the evaluation of disease activity and the appropriate treatment strategy. A cross-sectional descriptive study was carried out on 40 children, 37 girls (92%) and 3 boys (8%), with an average age of 11.7 years with lupus nephritis class III- IV in Vietnam National Children’s Hospital in 2019. The study results show that the average score of SLEDAI in the children with pericardial and pleural effusions was 20.94 ± 4.09; high blood pressure, 20.89 ± 4.23; and gross hematuria, 20.29 ± 5.03, which were higher than those in children without these manifestations with p< 0.05. The most common kidney manifestations were nephrotic-range nephritis with renal failure (40%) and Glomerulonephritis (35%), corresponding to an average SLEDAI score of 24.25 ± 5.52 and 24.33 ± 3.2, respectively (p = 0.001). SLEDAI had an inverse correlation with the C3 complement value (r -0.315, p <0.05). The average SLEDAI score decreased gradually from 18.75 ± 4.22 to 3.38 ± 3.95 points (p <0.001) after 12 months of treatment.  The study concludes that SLEDAI score was higher in patients with pleural and/or pericardial effusions, hypertension and gross hematuria, nephrotic-range nephritis with kidney failure or glomerulonephritis. SLEDAI score corresponded with the C3 complement value and the average SLEDAI score decreased gradually with treatment. Keywords: Lupus Nephritis class III- IV, SLEDAI. References [1] George Bertsias, Ricard Cervera và Dimitrios T Boumpas, Systemic Lupus Erythematosus: Pathogenesis and Clinical Features<sample chapter 20_mod 17_Systemic Lupus nephritis 2012.pdf> (2012), EULAR Textbook on Rheumatic Diseases, EULAR, 476-505.[2] D.M. Levy and S. Kamphuis, Systemic lupus erythematosus in children and adolescents. Pediatr Clin North Am59(2) (2012)345-64.[3] Thai Thien Nam, 2018, Lupus in National Children,s Hospital, [4] C.Bombardier, M.B. Hurwitz et al, Derivation of the SLEDAI: A disease activity index for lupus patients. The committee on prognosis studies in SLE, Arthritis Rheum 35(6) (1992) 630-640.[5] R. Shamim, S. Farman, S. Batool et al, Association of systemic lupus erythematosus disease activity index score with clinical and laboratory parameters in pediatric onset systemic lupus erythematosus. Pak J Med Sci. 36(3) (2020) 467-472.[6] Le Thuy Hang, Assesment of SLEDAI score and panthology in children with lupus nephritis, 2016, Pediatrician thesis, Hanoi Medical University.[7] S.K.S.M. Nazri, K.K. Wong and W.Z.W.A. Hamid, Pediatric systemic lupus erythematosus. Retrospective analysis of clinico-laboratory parameters and their association with Systemic Lupus Erythematosus Disease Activity Index score, Saudi Med J. 39(6) (2018) 627-631. [8] Nguyen Thuy Duong, clinical, paraclinical and pathology characteristics in children with nephritis caused by systemic lupus erythematosus, 2011, Master thesis, Hanoi Medical University.[9] S.N. Wong, W.K. Chan, J.Hui et al, Membranous lupus nephritis in Chinese children--a case series and review of the literature. Pediatr Nephrol, 24(10)(2009) 1989-1996.[10] N.T.N. Dung, H.T. Loan, S. Nielsen et al, Juvenile systemic lupus erythematosus onset patterns in Vietnamese children: a descriptive study of 45 children. Pediatric Rheumatology Online Journal, 10 (2010) 38-48.[11] T. Pusongchai, J. Jungthirapanich, S. Khositseth, Pediatric Systemic Lupus Erythematosus in Thammasat University Hospital, J Med Assoc Thai. 93(12) (2010) 283-290.    

scholarly journals Role of Neutrophil Extracellular Traps Regarding Patients at Risk of Increased Disease Activity and Cardiovascular Comorbidity in Systemic Lupus Erythematosus

2019 ◽  
Vol 47 (11) ◽  
pp. 1652-1660 ◽  
Author(s):  
Stanley Moore ◽  
Hsin-Hsuan Juo ◽  
Christoffer T. Nielsen ◽  
Helena Tyden ◽  
Anders A. Bengtsson ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
At Risk ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Severe Disease ◽  
Neutrophil Extracellular Traps ◽  
Systemic Lupus ◽  
Extracellular Traps ◽  
Patients At Risk

ObjectiveNeutrophil extracellular traps (NET) are essential in host defense, but are also linked to inflammation and autoimmunity, including in systemic lupus erythematosus (SLE). We recently described that immune complexes (IC) induce NET formation, promoting SLE-like disease in mice. In the current study, we investigated, for the first time to our knowledge, the role of NET in human SLE and their association with disease activity and severity.MethodsLevels of NET (myeloperoxidase-DNA complexes) were analyzed in plasma from 4 cross-sectional SLE cohorts (n = 44–142), 1 longitudinal SLE cohort (n = 47), and healthy individuals (n = 100) using ELISA. Type I interferon activity was determined using a cell reporter system.ResultsPatients with SLE had elevated levels of NET in circulation compared to healthy controls (p < 0.01). NET levels identified patients with a severe disease phenotype characterized by IC-driven nephritis (p < 0.05). Though not associated with current disease activity (p = 0.20), levels of NET were associated with future increase in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) within 3 months (OR 1.75, p = 0.01), as well as an overall heightened SLEDAI over 1 year (p < 0.01). Finally, levels of NET were associated with arterial events (OR 5.0, p = 0.02) and endothelial cell activation (p < 0.001).ConclusionNET levels are elevated in patients with SLE, associated with IC-driven disease. NET levels provide significant clinical value in identifying patients at risk of active disease and/or severe disease, including nephritis and cardiovascular disease, and may allow for early interventions.

scholarly journals Neutrophil Extracellular Traps Profiles in Patients with Incident Systemic Lupus Erythematosus and Lupus Nephritis

2019 ◽  
Vol 47 (3) ◽  
pp. 377-386 ◽  
Author(s):  
Maurizio Bruschi ◽  
Alice Bonanni ◽  
Andrea Petretto ◽  
Augusto Vaglio ◽  
Federico Pratesi ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Ex Vivo ◽  
Serum Levels ◽  
Neutrophil Extracellular Traps ◽  
Dnase Activity ◽  
Systemic Lupus ◽  
Net Production ◽  
Extracellular Traps

Objective.Neutrophil extracellular traps (NET) expose modified antigens for autoantibodies in vasculitis. Little is known about levels and removal pathways of NET in systemic lupus erythematosus (SLE), especially in lupus nephritis (LN). We determined circulating levels and defined NET removal in large subsets of patients with incident SLE (iSLE), some of whom had new-onset nephritis.Methods.Serum levels of NET (ELISA), DNase1/DNase1L3 (ELISA), and DNase activity (functional assay) were determined in 216 patients with iSLE [103 had incident LN (iLN)], in 50 patients with other primary glomerulonephritis, and in healthy controls. Ex vivo NET production by neutrophils purified from a random selection of patients was quantified as elastase/DNA release and by immunofluorescence techniques.Results.Serum NET levels were very high in iSLE/iLN compared to all groups of controls and correlated with anti-dsDNA, C3–C4, and proteinuria; iLN had the highest levels. DNase activity was decreased in iLN compared to SLE (20% had one-half DNase activity) despite similar serum levels of DNase1/DNase1L3. In these cases, pretreatment of serum with protein A restored DNase efficiency; 1 patient was homozygous for a c.289_290delAC variant of DNASE1L3. Ex vivo NET production by neutrophils purified from LN, SLE, and normal controls was similar in all cases.Conclusion.Patients with iLN have increased circulating NET and reduced DNase activity, the latter being explained by the presence of inhibitory substances in circulation and/or by rare DNase1L3 mutations. Accumulation of NET derives from a multifactorial mechanism, and is associated and may contribute to disease severity in SLE, in particular to renal lesions. (Clinical trial registration: The Zeus study was registered at ClinicalTrials.gov, study number NCT02403115).

scholarly journals The enrichment of neutrophil extracellular traps impair the placentas of systemic lupus erythematosus through accumulating decidual NK cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Meng Jiang ◽  
Nan Shen ◽  
Haibo Zhou ◽  
You Wang ◽  
Sihan Lin ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Nk Cells ◽  
Lupus Erythematosus ◽  
Neutrophil Extracellular Traps ◽  
Clinical Samples ◽  
Systemic Lupus ◽  
Extracellular Traps ◽  
Fetal Birth Weight ◽  
Immunological Disorder ◽  
Adverse Pregnancy

AbstractDespite the advances made in the management of pregnancies in women with systemic lupus erythematosus (SLE), the rate of adverse pregnancy outcomes is still higher than that in the general population. In the last few years, neutrophil extracellular traps (NETs) were proven to be detrimental in both autoimmune diseases and placental injury. We investigated whether NETs could be detected in the placentas of pregnant individuals with SLE and explored the relationship between NETs and decidual natural killer cells (dNKs), which comprise the majority of immune cells at the maternal–fetal interface, using clinical samples and animal models. In this study, we found that the infiltration of NETs and dNKs, especially CD56+CD16+ NK cells, was significantly increased in pregnant individuals with SLE with placental insufficiency. In the murine models of SLE, the number of dNKs was significantly decreased due to the decreased formation of NETs affected by Ly6G. Moreover, the histopathological placental injury was reduced, with a remarkable increase in fetal birth weight. This study shows that NETs may contribute to immunological disorder in the placenta and the pathological changes in pregnancies with SLE, which provides a research basis for further explorations of the mechanism of SLE in placental impairment.

Serum uric acid as a predictor for nephritis in Egyptian patients with systemic lupus erythematosus

Lupus ◽  
2020 ◽  
pp. 096120332097904
Author(s):  
Eman Ahmed Hafez ◽  
Sameh Abd El-mottleb Hassan ◽  
Mohammed Abdel Monem Teama ◽  
Fatma Mohammed Badr
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Renal Function ◽  
Uric Acid ◽  
Lupus Nephritis ◽  
Serum Creatinine ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Group 2 ◽  
Group 1

Objective Lupus nephritis (LN) is closely associated with hyperuricemia, and uric acid is considered a risk factor for renal involvement in systemic lupus erythematosus (SLE). This study aimed to examine the association between serum uric acid (SUA) level and LN development and progression in SLE patients with normal renal function. Methods A total of 60 SLE patients with normal renal function from Ain Shams University Hospital were selected and assigned to group 1 (30 patients with LN) and group 2 (30 patients without LN). All patients were subjected to history taking, clinical examination, disease activity assessment based on SLE disease activity index (SLEDAI) and renal SLEDAI (SLEDAI-R) scores, and laboratory investigations, including as SUA, complete blood count, blood urea nitrogen (BUN), serum creatinine, creatinine clearance, urine analysis, protein/creatinine ratio, 24-h urinary protein excretion, Antinuclear antibodies (ANA), anti-dsDNA antibody, and serum complement (C3, C4). Results Disease duration, SLEDAI score, and SUA level were higher in group 1 than in group 2 (p < 0.001). SUA level was positively correlated with SLEDAI and SLEDAI-R scores, proteinuria, urinary casts, renal biopsy class, disease activity and chronicity indices, BUN level, and serum creatinine level but was negatively correlated with creatinine clearance (p < 0.05). SUA was a predictor of LN development in SLE patients (sensitivity, 83.3%; specificity, 70%). Conclusion SUA is associated with the development of lupus nephritis in patients with normal kidney function also SUA in-dependently correlated with disease activity and chronicity in LN.

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