scholarly journals Intermittent Fasting Aggravates Lupus Nephritis through Increasing Survival and Autophagy of Antibody Secreting Cells in MRL/lpr Mice

2020 ◽  
Vol 21 (22) ◽  
pp. 8477
Author(s):  
Seung-Min Hong ◽  
Jaeseon Lee ◽  
Se Gwang Jang ◽  
Youngseok Song ◽  
Minjun Kim ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Lupus Nephritis ◽  
Immune Complex ◽  
Lupus Erythematosus ◽  
Plasma Cells ◽  
Clinicopathological Parameters ◽  
Control Group ◽  
Intermittent Fasting ◽  
Glomerular Injury ◽  
Dsdna Antibody

Systemic lupus erythematosus (SLE) is an autoimmune disease in which the main contributors to organ damage are antibodies against autoantigens, such as double-stranded DNA (dsDNA). Calorie restriction and intermittent fasting (IF) have been shown to improve autoimmune disease symptoms in patients and animal models. Here, we tested the hypothesis that IF might improve symptoms in MRL/lpr mice, which spontaneously develop an SLE-like disease. Groups of mice were fed every other day (IF) or provided food ad libitum (controls), and various lupus-associated clinicopathological parameters were analyzed for up to 28 weeks. Contrary to expectations, anti-dsDNA antibody levels, immune complex deposition in the kidney, and glomerular injury were higher in the IF group than the control group, although there were no differences in spleen and lymph node weights between groups. Proteinuria was also worsened in the IF group. IF also increased the abundance of B cells, plasmablasts, and plasma cells and elevated autophagy in plasma cells in the spleen and lymph nodes. Secretion of anti-dsDNA antibody by splenocytes in vitro was reduced by chloroquine-induced inhibition of autophagy. These results suggest that IF exacerbates lupus nephritis in MRL/lpr mice by increasing autoantibody immune complex formation.

TLR4+CXCR4+ plasma cells drive nephritis development in systemic lupus erythematosus

2018 ◽  
Vol 77 (10) ◽  
pp. 1498-1506 ◽  
Author(s):  
Kongyang Ma ◽  
Jingyi Li ◽  
Xiaohui Wang ◽  
Xiang Lin ◽  
Wenhan Du ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Immune Complex ◽  
Lupus Erythematosus ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Renal Tissue ◽  
Systemic Lupus ◽  
Autoantibody Production

ObjectivesIn patients with systemic lupus erythematosus (SLE), immune tolerance breakdown leads to autoantibody production and immune-complex glomerulonephritis. This study aimed to identify pathogenic plasma cells (PC) in the development of lupus nephritis.MethodsPC subsets in peripheral blood and renal tissue of patients with SLE and lupus mice were examined by flow cytometry and confocal microscopy, respectively. Sorting-purified PCs from lupus mice were adoptively transferred into Rag2-deficient recipients, in which immune-complex deposition and renal pathology were investigated. In culture, PCs from lupus mice and patients with SLE were treated with a TLR4 inhibitor and examined for autoantibody secretion by enzyme-linked immunospot assay (ELISPOT). Moreover, lupus mice were treated with a TLR4 inhibitor, followed by the assessment of serum autoantibody levels and glomerulonephritis activity.ResultsThe frequencies of TLR4+CXCR4+ PCs in peripheral blood and renal tissue were found significantly increased with the potent production of anti-dsDNA IgG, which were associated with severe renal damages in patients with SLE and mice with experimental lupus. Adoptive transfer of TLR4+CXCR4+ PCs from lupus mice led to autoantibody production and glomerulonephritis development in Rag2-deficient recipients. In culture, TLR4+CXCR4+ PCs from both lupus mice and patients with SLE showed markedly reduced anti-dsDNA IgG secretion on TLR4 blockade. Moreover, in vivo treatment with TLR4 inhibitor significantly attenuated autoantibody production and renal damages in lupus mice.ConclusionsThese findings demonstrate a pathogenic role of TLR4+CXCR4+ PCs in the development of lupus nephritis and may provide new therapeutic strategies for the treatment of SLE.

scholarly journals Amiselimod (MT-1303), a Novel Sphingosine 1-Phosphate Receptor-1 Modulator, Potently Inhibits the Progression of Lupus Nephritis in Two Murine SLE Models

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Kunio Sugahara ◽  
Yasuhiro Maeda ◽  
Kyoko Shimano ◽  
Mikako Murase ◽  
Sachiko Mochiduki ◽  
...  
Keyword(s):  
T Cells ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Plasma Cells ◽  
Glomerular Sclerosis ◽  
Therapeutic Effects ◽  
Dsdna Antibody ◽  
Sphingosine 1 Phosphate ◽  
Murine Systemic Lupus Erythematosus ◽  
Antibody Levels

Amiselimod (MT-1303) is a novel and selective sphingosine 1-phosphate receptor-1 (S1P1) modulator with a more favorable cardiac safety profile than other S1P1 receptor modulators. In this study, we evaluated the effects of MT-1303 on the progression of lupus nephritis in two well-known murine systemic lupus erythematosus (SLE) models, MRL/lpr and NZBWF1 mice, compared with those of FK506. Daily oral doses of 0.1 and 0.3 mg/kg MT-1303 not only inhibited the development of lupus nephritis when administered before onset in MRL/lpr and NZBWF1 mice but also improved symptoms of lupus nephritis when administered after onset in MRL/lpr mice. Its efficacy in these models was more potent or comparable to that of FK506 (1 and 3 mg/kg). In histological analysis, treatment with MT-1303 inhibited infiltration of T cells into the kidneys, mesangial expansion, and glomerular sclerosis. MT-1303 treatment resulted in a marked reduction in T cells and B cells in the peripheral blood and significantly inhibited increases in the number of plasma cells in the spleen and T cells in the kidneys. In addition, administration of MT-1303 suppressed elevations in serum anti-dsDNA antibody levels in MRL/lpr mice, but not in NZBWF1 mice. Our findings show that MT-1303 exhibits marked therapeutic effects on lupus nephritis in two SLE models, likely by reducing the infiltration of autoreactive T cells into the kidneys. These results suggest that MT-1303 has the potential to be used as a therapeutic agent for patients suffering from SLE, including lupus nephritis.

scholarly journals Case Report: A Rare Case of Lupus Nephritis Associated With Mantle Cell Lymphoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Daorina Bao ◽  
Ying Tan ◽  
Xiaojuan Yu ◽  
Bingjie Wang ◽  
Hui Wang ◽  
...  
Keyword(s):  
Renal Function ◽  
Lupus Nephritis ◽  
Mantle Cell Lymphoma ◽  
Lupus Erythematosus ◽  
Rare Case ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoid Cells ◽  
Glomerular Injury ◽  
Mantle Cell

In this research, we described a very rare case of secondary lupus nephritis associated with B-cell lymphoma. An 84-year-old man was hospitalized at our institute for lower extremity edema persisting for over 2 months. He was diagnosed with systemic lupus erythematosus based on clinical and laboratory criteria, which showed impaired renal function and nephrotic syndrome with predominant hematuria. Renal biopsy showed IV+V lupus nephritis with highly infiltrated lymphoid cells in the kidney. Secondary lupus nephritis was suspected based on the possible pathogenesis of glomerular injury due to mantle cell lymphoma. Low-dose dexamethasone, rituximab, and lenalidomide were immediately started on the patient, and his renal function was improved after the first cycle of chemotherapy.

scholarly journals Podocyte Injury in Lupus Nephritis

2019 ◽  
Vol 8 (9) ◽  
pp. 1340 ◽  
Author(s):  
Hamza Sakhi ◽  
Anissa Moktefi ◽  
Khedidja Bouachi ◽  
Vincent Audard ◽  
Carole Hénique ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Glomerular Injury ◽  
Crescent Formation ◽  
Podocyte Injury ◽  
Inflammatory Processes ◽  
Lupus Podocytopathy ◽  
Parietal Epithelial Cells ◽  
Lupus Glomerulonephritis

Systemic lupus erythematosus (SLE) is characterized by a broad spectrum of renal lesions. In lupus glomerulonephritis, histological classifications are based on immune-complex (IC) deposits and hypercellularity lesions (mesangial and/or endocapillary) in the glomeruli. However, there is compelling evidence to suggest that glomerular epithelial cells, and podocytes in particular, are also involved in glomerular injury in patients with SLE. Podocytes now appear to be not only subject to collateral damage due to glomerular capillary lesions secondary to IC and inflammatory processes, but they are also a potential direct target in lupus nephritis. Improvements in our understanding of podocyte injury could improve the classification of lupus glomerulonephritis. Indeed, podocyte injury may be prominent in two major presentations: lupus podocytopathy and glomerular crescent formation, in which glomerular parietal epithelial cells play also a key role. We review here the contribution of podocyte impairment to different presentations of lupus nephritis, focusing on the podocyte signaling pathways involved in these lesions.

P0080INTERLEUKIN-17A GENE POLYMORPHISM (RS2275913G>A) IN SLE PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Nehal Atef elshabrawy ◽  
Hussein Sheashaa ◽  
Adel L Abdelsalam ◽  
Ahmed Mohammed Abd El Wahab
Keyword(s):  
Lupus Nephritis ◽  
Gene Polymorphism ◽  
Inflammatory Diseases ◽  
Statistical Significance ◽  
Group Versus ◽  
University Hospital ◽  
Control Group ◽  
Cross Sectional ◽  
Dsdna Antibody ◽  
Significant Difference

Abstract Background and Aims There are six IL-17-family ligands [IL-17A, IL-17B, IL-17C, IL-17D, IL-17E (IL-25) and IL-17F]. Interleukin-17A (IL-17A) also commonly called IL-17, is produced by the T helper17 (Th17) subset of CD4+ T cells.Interleukin-17 and other Th17 cytokines are linked to the pathogenesis of diverse autoimmune and inflammatory diseases. IL-17A is detected in synovial fluids and synovium from RA patients and induces proinflammatory cytokine production from synoviocytes, also expression of IL-17A was higher in SLE patients and its level positively correlated with the severity of lupus nephritis, because of its contribution to increasing anti-double-stranded DNA (dsDNA) antibody production in SLE. The aim of the present study is to determine the IL-17A gene polymorphism (rs2275913 G>A) frequency in patients with SLE and lupus nephritis, and to determine the association of this polymorphism with the disease activity. Method This cross-sectional, observational, case control study was carried out on 50 females patients, with their age ranged from 15 to 50 years (mean 25.67±9.29 years) with SLE attending Mansoura University Hospital .A control group of 50 healthy females of matched age were also included. The patient group was subdivided into patients with and those without lupus Nephritis (35 and 15 patients, respectively). Lupus nephritis was confirmed by renal biopsy. All patients were subjected to a thorough clinical evaluation and routine laboratory tests. SLEDAI score was calculated for all patients to determine the degree of lupus activity. DNA extraction was performed for all patients as well as controls, One SNPs of IL-17A (rs2275913G>A) was genotyped utilizing PCR- RFLP technique. Results The frequency of rs2275913 A allele was significantly higher in SLE patients than the control group (34.0% vs. 21.0%, respectively; p=0.04, OR =1.9, 95%CI =1.03-3.65). While G allele was significantly higher in control group, (P=0.04)). Moreover, AA genotype was significantly higher in the SLE patients than in the control group (8.0% vs. 0.0%, respectively; p=0.036) and associated with higher SLEDAI, ANA, and anti-dsDNA antibodies titer, (P=0.03, P=.039, P=0.047 respectively).on the other hand there was no significant difference in GG and GA genotypes in the SLE patients versus the control group. The frequency of both genotype GA and AA was higher in the SLE patients than the controls (60% vs. 42%, respectivley; OR=2.07, CI-95%=0.9-5.59); although the difference was not statistically significant (P= 0.07).Although A allele was numerically higher in lupus nephritis group versus non nephritis group(37.0% vs 27.0%, respectively), the Analysis of the frequency of IL-17A rs2275913 alleles and genotypes showed no statistical differences between the two groups. Moreover there was no statistical significance between different genotypes in cases of nephritis regard lupus nephritis class (P=0.9) and no statistical significance between different genotypes (GG-GA-AA) regarding activity indices (AI) or chronicity indices (CI) in lupus nephritis group (P=0.18, P=0.56 respectively). Conclusion We suggest that there was a significant association between IL-17A rs2275913 G>A polymorphism and SLE, as A allele and AA genotype were increased in SLE patients, lupus nephritis especially those with high activity

scholarly journals Niclosamide Suppresses the Expansion of Follicular Helper T Cells and Alleviates Disease Severity in Two Murine Models of Lupus via STAT3

2020 ◽  
Author(s):  
Se Gwang Jang ◽  
Jaeseon Lee ◽  
Seung-Min Hong ◽  
Young-Seok Song ◽  
Min Jun Kim ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Plasma Cells ◽  
Immune Cell ◽  
Parasitic Infections ◽  
Therapeutic Effects ◽  
Murine Models ◽  
Autoantibody Production ◽  
Follicular Helper ◽  
Dsdna Antibody ◽  
Models Of Lupus

Abstract Background. Autoantibody production against endogenous cellular components is pathogenic feature of systemic lupus erythematosus (SLE). Follicular helper T (TFH) cells aid in B cell differentiation into autoantibody-producing plasma cells (PCs). The IL-6 and IL-21 cytokine-mediated STAT3 signaling are crucial for the differentiation to TFH cells. Niclosamide is an anti-helminthic drug used to treat parasitic infections but also exhibits a therapeutic effect on autoimmune diseases due to its potential immune regulatory effects. In this study, we examined whether Niclosamide treatment could relieve lupus-like autoimmunity by modulating the differentiation of TFH cells in two murine models of lupus.Methods. 10-week-old MRL/lpr mice were orally administered with 100 mg/kg of Niclosamide or with 0.5% methylcellulose (MC, vehicle) daily for 7 weeks. TLR7 agonist, resiquimod was topically applied to an ear of 8-week-old C57BL/6 mice 3 times a week for 5 weeks. And they were orally administered with 100 mg/kg of Niclosamide or with 0.5% MC daily for 5 weeks. Every mouse was analyzed for lupus nephritis, proteinuria, autoantibodies, immune complex, immune cell subsets at the time of the euthanization.Results. Niclosamide treatment greatly improved proteinuria, anti-dsDNA antibody levels, immunoglobulin subclass titers, histology of lupus nephritis, and C3 deposition in MRL/lpr and R848-induced mice. In addition, Niclosamide inhibited the proportion of TFH cells and PCs in the spleens of these animals, and effectively suppressed differentiation of TFH-like cells and expression of associated genes in vitro.Conclusions. Niclosamide exerted therapeutic effects on murine lupus models by suppressing TFH cells and plasma cells through STAT3 inhibition.

scholarly journals N-acetylcysteine effectively alleviates systemic lupus erythematosus in mice via regulation of oxidative stress

2021 ◽  
Vol 19 (12) ◽  
pp. 2591-2595
Author(s):  
Feng Lu ◽  
Bingxin Liu ◽  
Hui Zhao
Keyword(s):  
Oxidative Stress ◽  
Systemic Lupus Erythematosus ◽  
Superoxide Dismutase ◽  
Lupus Erythematosus ◽  
Serum Levels ◽  
Control Group ◽  
Systemic Lupus ◽  
Urine Protein ◽  
Treatment Groups ◽  
Dsdna Antibody

Purpose: To study the influence of N-acetylcysteine (NAC) on systemic lupus  erythematosus (SLE) mice, and the mechanism(s) involved. Methods: Fourteen MRL/lpr SLE mice aged 5 weeks (mean weight = 20.35 ± 2.12 g) were divided into two 7-mouse groups: SLE (control) and treatment groups. The control group comprised healthy female SPF-grade C57BL/6 mice (n = 7). The treatment group mice received intraperitoneal injection of NAC at a dose of 250 mg/kg daily for 8 weeks. The serum levels of malondialdehyde (MDA) and nitric oxide (NO), and activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD), were assayed using standard methods. The level of urine protein and activity of anti-double stranded (ds) DNA antibody were determined using their respective enzyme-linked assay (ELISA) kits. Results: The spleens of mice in SLE mice were significantly enlarged, relative to control mice, but they were reduced significantly by NAC (p < 0.05). N-Acetylcysteine (NAC) also significantly reduced the serum levels of MDA and NO in SLE mice, but significantly  increased the serum activities of superoxide dismutase and GPx. Moreover, urine protein concentration and activity of anti-dsDNA antibody in SLE mice significantly increased, but reduced significantly by NAC treatment (p < 0.05). Conclusion: These results suggest that NAC effectively alleviates SLE in mice via regulation of oxidative stress. Thus, NAC has the potentials for development into a therapy for the management of SLE. Keywords: Anti-dsDNA antibodies, Antioxidant enzymes, N-acetylcysteine, Oxidative stress, Systemic lupus erythematosus

scholarly journals Potentiation of Lupus Activity by Granulocyte Colony-Stimulating Factor

2021 ◽  
pp. 1-5
Author(s):  
Tsz Ching Mok ◽  
Lok Ping Ng ◽  
Eva Tsz Fung Chui ◽  
Ho Yin Chung
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Autoimmune Disease ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Neutrophil Apoptosis ◽  
Cytokine Storm ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Systemic Lupus ◽  
Stimulating Factor

Recombinant human granulocyte colony-stimulating factor (G-CSF) is commonly used to accelerate recovery of neutropenia in patients with marrow suppression. We hereby report a patient with systemic lupus erythematosus (SLE) who developed diffuse lupus nephritis and impending cytokine storm after G-CSF therapy. The exact mechanisms by which G-CSF leads to lupus flares remains enigmatic. Increased neutrophil apoptosis and release of cytokines have been postulated. The use of G-CSF in patients with autoimmune disease should be cautious.

scholarly journals Predominant Mesangial IgM, C3 and λ Light Chain Depositions and Interstitial Nephritis in a Patient with Overlap Syndrome and Positivity for Anti-Mitochondrial M2 Antibody: A Case Report

2021 ◽  
Author(s):  
Saeko Yamada ◽  
Hiroko Kanda ◽  
Hiroyuki Abe ◽  
Yukako Shintani Domoto ◽  
Ryochi Yoshida ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Renal Dysfunction ◽  
Interstitial Nephritis ◽  
Light Chain ◽  
Lupus Erythematosus ◽  
Plasma Cells ◽  
Overlap Syndrome ◽  
Pathological Findings ◽  
Glucocorticoid Treatment ◽  
Λ Light Chain

Abstract Overlap syndrome refers to a group of conditions that have clinical features of more than one well-characterized rheumatic disease and meet the respective classification criteria. There are no typical renal histological findings in overlap syndrome. When patients with overlap syndrome develop renal dysfunction, various potential causes, including lupus nephritis (LN), renal crisis by systemic sclerosis, interstitial nephritis and so on, need to be distinguished. Here we report a 44-year-old woman with overlap syndrome involving systemic lupus erythematosus (SLE), diffuse cutaneous systemic scleroderma and Sjogren’s syndrome, who was also positive for anti-mitochondrial M2 antibody. She developed glomerular hematuria, proteinuria and increase in creatinine appeared gradually. Suspecting lupus nephritis, renal biopsy was performed. However, in the interstitium, mild infiltration of lymphocytes and plasma cells and very partial fibrosis were observed. Immunofluorescence (IF) microscopy revealed predominant mesangial IgM, C3 and λ light chain staining. Overall, LN was not diagnosed based on these findings. Renal dysfunction was normalized by glucocorticoid treatment for three months. This case suggests the importance of a renal diagnosis based on renal pathological findings, especially in a case of overlap syndrome including SLE.

Abstract 008: Depletion of Antibody-Secreting Plasma Cells Attenuates Hypertension in an Experimental Model of Autoimmune Disease

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Erin B Taylor ◽  
Michael J Ryan
Keyword(s):  
Lupus Erythematosus ◽  
Plasma Cells ◽  
Urinary Albumin Excretion ◽  
Primary Source ◽  
Autoimmune Disorder ◽  
Glomerular Injury ◽  
Autoantibody Production ◽  
Bortezomib Treatment ◽  
Anti Cd20 ◽  
And Control

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that is characterized by aberrant immunoglobulin (Ig) production, notably pathogenic autoantibodies, and is associated with prevalent hypertension, renal injury, and cardiovascular disease. Recent studies by our laboratory have shown that chronic B cell depletion with anti-CD20 monoclonal antibody reduces autoantibody production and prevents the development of hypertension in an experimental female mouse model of SLE (NZBWF1). However, the treatment was only effective when administered before the onset of autoantibody production. Because long-lived plasma cells produce the majority of serum Ig and are the primary source of autoantibodies in SLE, we hypothesized that depletion of plasma cells using the proteasome inhibitor bortezomib would lower autoantibody production and attenuate hypertension. Thirty week old female NZBWF1 and control (NZW) mice were injected i.v. with vehicle (0.9% saline) or bortezomib (0.75 mg/kg) twice weekly for four weeks. Percentages of CD138 + intracellular-κ light chain + plasma cells in the bone marrow were lower in bortezomib treated SLE mice compared to vehicle-treated SLE mice (1.7±0.19% vs. 0.95±0.18%, p<0.05), as assessed by flow cytometry. Total plasma IgG was higher in SLE mice as compared to control mice (5.02±1.2 mg/mL vs. 2.88±0.78, p<0.05), and were lower in SLE mice treated with bortezomib (1.5±0.5 mg/mL, p<0.05 vs. SLE-vehicle). In addition, bortezomib treatment reduced circulating anti-dsDNA IgG levels in SLE mice (OD450 1.36±0.25 vs. 0.44±0.11 p<0.01). Urinary albumin excretion, an indicator of glomerular injury, was increased in SLE mice as compared to control mice (16.8±10.1 vs. 0.015±0.002 mg/day, p<0.05) and was lower in SLE mice treated with bortezomib (0.24±00.16 mg/day, p<0.05 vs. SLE-vehicle). Mean arterial pressure (MAP; mmHg) measured in conscious mice by carotid artery catheter was higher in SLE mice than in control mice (142±5 vs. 118±3, p<0.001). MAP was significantly lower in SLE mice treated with bortezomib when compared to vehicle treated mice (119±4 vs. 142±5, p<0.001). These data suggest that production of autoantibodies by plasma cells in SLE mechanistically contribute to the pathogenesis of hypertension.

Sign in / Sign up

Export Citation Format

Share Document