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systemic lupus , glomerulonephritis

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https://www.readbyqxmd.com/read/27880975/ror%C3%AE-t-expression-in-tregs-promotes-systemic-lupus-erythematosus-via-il-17-secretion-alteration-of-treg-phenotype-and-suppression-of-th2-responses
#1
Malte A Kluger, Anna Nosko, Torben Ramcke, Boeren Goerke, Matthias C Meyer, Claudia Wegscheid, Michael Luig, Gisa Tiegs, Rolf A K Stahl, Oliver M Steinmetz
Systemic lupus erythematosus (SLE) is a common autoimmune disorder with a complex and poorly understood immuno-pathogenesis. However, a pathogenic role for the Th17 axis was demonstrated by many studies, while Tregs were shown to mediate protection. Recently, we and others characterized a novel and independent T cell population expressing both, the Treg characteristic transcription factor Foxp3 and the Th17 defining RORγt. Studies in a model of acute glomerulonephritis unveiled potent regulatory, but in addition also pro-inflammatory functions of RORγt(+) Foxp3(+) Tregs...
November 23, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27858870/simultaneous-comprehensive-multiplex-autoantibody-analysis-for-rapidly-progressive-glomerulonephritis
#2
Mandy Sowa, Barbara Trezzi, Rico Hiemann, Peter Schierack, Kai Grossmann, Juliane Scholz, Valentina Somma, Renato Alberto Sinico, Dirk Roggenbuck, Antonella Radice
Rapidly progressive glomerulonephritis (RPGN) is mainly caused by anti-glomerular basement membrane (GBM) antibody-mediated glomerulonephritis, immune-complex or anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides and leads to rapid loss of renal function. Detection of ANCA and autoantibodies (autoAbs) to GBM and dsDNA enables early diagnosis and appropriate treatment of RPGN aiding in preventing end-stage renal disease.Determination of ANCA on neutrophils (ANCA) as well as autoAbs to myeloperoxidase (MPO-ANCA), proteinase 3 (PR3-ANCA), GBM, and dsDNA was performed by the novel multiplex CytoBead technology combining cell- and microbead-based autoAb analyses by automated indirect immunofluorescence (IIF)...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27817791/-advances-in-clinical-research-on-c1q-nephropathy
#3
Juan Yang, Bi-Li Zhang
C1q nephropathy is a rare type of glomerulonephritis manifested as the deposition of C1q in the glomerular mesangium during immunofluorescent staining. Systemic lupus erythematosus and type I membranoproliferative glomerulonephropathy need to be excluded in the diagnosis of C1q nephropathy. C1q nephropathy has various manifestations under a light microscope, mainly including minimal change disease, focal segmental glomerulosclerosis, and proliferative glomerulonephritis. This disease is mainly manifested as persistent proteinuria or nephrotic syndrome and occurs more frequently in boys...
November 2016: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/27716443/a-discrete-cluster-of-urinary-biomarkers-discriminates-between-active-systemic-lupus-erythematosus-patients-with-and-without-glomerulonephritis
#4
Carolina Landolt-Marticorena, Stephenie D Prokopec, Stacey Morrison, Babak Noamani, Dennisse Bonilla, Heather Reich, James Scholey, Carmen Avila-Casado, Paul R Fortin, Paul C Boutros, Joan Wither
BACKGROUND: Management of lupus nephritis (LN) would be greatly aided by the discovery of biomarkers that accurately reflect changes in disease activity. Here, we used a proteomics approach to identify potential urinary biomarkers associated with LN. METHODS: Urine was obtained from 60 LN patients with paired renal biopsies, 25 active non-LN SLE patients, and 24 healthy controls. Using Luminex, 128 analytes were quantified and normalized to urinary creatinine levels...
October 4, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27680869/icer-is-requisite-for-th17-differentiation
#5
Nobuya Yoshida, Denis Comte, Masayuki Mizui, Kotaro Otomo, Florencia Rosetti, Tanya N Mayadas, José C Crispín, Sean J Bradley, Tomohiro Koga, Michihito Kono, Maria P Karampetsou, Vasileios C Kyttaris, Klaus Tenbrock, George C Tsokos
Inducible cAMP early repressor (ICER) has been described as a transcriptional repressor isoform of the cAMP response element modulator (CREM). Here we report that ICER is predominantly expressed in Th17 cells through the IL-6-STAT3 pathway and binds to the Il17a promoter, where it facilitates the accumulation of the canonical enhancer RORγt. In vitro differentiation from naive ICER/CREM-deficient CD4(+) T cells to Th17 cells is impaired but can be rescued by forced overexpression of ICER. Consistent with a role of Th17 cells in autoimmune and inflammatory diseases, ICER/CREM-deficient B6...
September 29, 2016: Nature Communications
https://www.readbyqxmd.com/read/27669412/immune-mediated-nephropathy-and-systemic-autoimmunity-in-mice-does-not-require-receptor-interacting-protein-kinase-3-ripk3
#6
Chelsea Corradetti, Neelakshi R Jog, Stefania Gallucci, Michael Madaio, Siddharth Balachandran, Roberto Caricchio
Immune mediated nephropathy is one of the most serious manifestations of lupus and is characterized by severe inflammation and necrosis that, if untreated, eventually leads to renal failure. Although lupus has a higher incidence in women, both sexes can develop lupus glomerulonephritis; nephritis in men develops earlier and is more severe than in women. It is therefore important to understand the cellular and molecular mechanisms mediating nephritis in each sex. Previous work by our lab found that the absence or pharmacological inhibition of Poly [ADP-ribose] polymerase 1 (PARP-1), an enzyme involved in DNA repair and necrotic cell death, affects only male mice and results in milder nephritis, with less in situ inflammation, and diminished incidence of necrotic lesions, allowing for higher survival rates...
2016: PloS One
https://www.readbyqxmd.com/read/27666815/role-of-galectin-3-in-autoimmune-and-non-autoimmune-nephropathies
#7
Francesca Saccon, Mariele Gatto, Anna Ghirardello, Luca Iaccarino, Leonardo Punzi, Andrea Doria
Galectins are evolutionary conserved β-galactoside binding proteins with a carbohydrate-recognition domain (CRD) of approximately 130 amino acids. In mammals, 15 members of the galectin family have been identified and classified into three subtypes according to CRD organization: prototype, tandem repeat-type and chimera-type galectins. Galectin-3 (gal-3) is the only chimera type galectin in vertebrates containing one CRD linked to an unusual long N-terminal domain which displays non-lectin dependent activities...
September 23, 2016: Autoimmunity Reviews
https://www.readbyqxmd.com/read/27629736/the-safety-of-intravenous-cyclophosphamide-in-the-treatment-of-rheumatic-diseases
#8
Patryk J Woytala, Ewa Morgiel, Anna Łuczak, Katarzyna Czesak-Woytala, Piotr Wiland
BACKGROUND: The therapeutic effects of cyclophosphamide (CP) in the treatment of systemic rheumatic diseases are related to its immune suppressive activity. However effective, the application of CP is restricted due to multiple adverse effects. OBJECTIVES: This retrospective study was conducted to determine the frequency of adverse effects attributed to CP toxicity. MATERIAL AND METHODS: The study involved 65 patients (17 male; 48 female) receiving intravenous CP between October 2007 and December 2010...
May 2016: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/27606473/association-between-severe-disease-course-and-nephritis-with-q222r-polymorphism-in-dnase-i-gene-among-lupus-patients-an-argentine-multicenter-study
#9
G Camicia, S A Muñoz, A Allievi, A O Orden, S Perés Wingeyer, R Trobo, A Eimon, J C Barreira, E Schneeberger, J Sarano, J Hofman, G de Larrañaga, F Aranda
UNLABELLED: Objetives: Systemic lupus erythematosus is a multifactorial autoimmune disease and the glomerulonephritis is one of the most severe complications, which leads to severe persistent proteinuria, chronic renal failure, and end-stage renal disease. This multicenter study investigated the genetic associations of a non-synonymous single-nucleotide polymorphism in DNase I with the risk of lupus and its influence on development of nephropathy in an Argentinean population. METHODS: Using the Polymerase chain reaction restriction fragment length polymorphism method, the Q222R (+2373A→G; Gln244Arg) DNase I polymorphism was studied in 156 systemic lupus erythematosus patients and 170 healthy controls...
April 2016: Acta Reumatológica Portuguesa
https://www.readbyqxmd.com/read/27569461/-clinical-guideline-for-the-treatment-of-lupus-nephritis-and-single-centre-results-of-mycofenolate-mofetil-among-patients-with-lupus-nephritis-in-the-national-institute-of-rheumatology-and-physiotherapy-budapest
#10
Melinda Zsuzsanna Szabó, Emese Kiss
The authors present the latest guideline for the treatment of lupus nephritis and their own single-centre results with mycofenolate mofetil treated lupus nephritis. Lupus nephritis and mainly its proliferative form is a frequent and potentially life-threatening manifestation of systemic lupus erythematosus that can lead to end-stage renal disease. The treatment of lupus nephritis greatly improved in the last decades; mycofenolate mofetil has become an alternative of cyclophosphamide both in remission induction and as a maintenance regimen as well in the treatment of Class III and IV glomerulonephritis...
August 2016: Orvosi Hetilap
https://www.readbyqxmd.com/read/27527599/opposing-roles-of-tyrosine-kinase-receptors-mer-and-axl-determine-clinical-outcomes-in-experimental-immune-mediated-nephritis
#11
Yuxuan Zhen, Stephen O Priest, Wen-Hai Shao
Glomerulonephritis is one of the most severe manifestations of systemic lupus erythematosus, with considerable morbidity and mortality. There remains a major unmet need for successful management of lupus nephritis. TAM family receptor tyrosine kinases (Mer and Axl) play an important role in the maintenance of immune homeostasis in the kidney. Mer is constitutively expressed in the glomeruli; Axl expression is inducible in glomeruli under inflammatory conditions. To investigate the distinct functions of Axl and Mer in lupus nephritis, we compared the severity of nephrotoxic serum glomerulonephritis in wild-type (WT), Axl-knockout (KO), Mer-KO, and Axl/Mer-KO mice...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27527596/essential-requirement-for-ifn-regulatory-factor-7-in-autoantibody-production-but-not-development-of-nephritis-in-murine-lupus
#12
Fumi Miyagawa, Yutaka Tagaya, Keiko Ozato, Hideo Asada
Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease characterized by the production of autoantibodies against nuclear components. Recent genetic studies of SLE patients have revealed that IFN regulatory factor (IRF) 7 gene polymorphisms are associated with an increased risk of SLE, but the precise role of IRF7 in SLE development is not fully understood. We investigated the role of IRF7 in the pathogenesis of SLE using a mouse model and saw a curious dissociation of autoantibody production and development of glomerulonephritis...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27513935/silica-triggered-autoimmunity-in-lupus-prone-mice-blocked-by-docosahexaenoic-acid-consumption
#13
Melissa A Bates, Christina Brandenberger, Ingeborg I Langohr, Kazuyoshi Kumagai, Adam L Lock, Jack R Harkema, Andrij Holian, James J Pestka
Occupational exposure to respirable crystalline silica (cSiO2, quartz) is etiologically linked to systemic lupus erythematosus (lupus) and other human autoimmune diseases (ADs). In the female NZBWF1 mouse, a widely used animal model that is genetically prone to lupus, short-term repeated intranasal exposure to cSiO2 triggers premature initiation of autoimmune responses in the lungs and kidneys. In contrast to cSiO2's triggering action, consumption of the ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) prevents spontaneous onset of autoimmunity in this mouse strain...
2016: PloS One
https://www.readbyqxmd.com/read/27468526/post-infectious-glomerulonephritis-in-pediatric-patients-over-two-decades-severity-associated-features
#14
Rona Dagan, Roxana Cleper, Miriam Davidovits, Levana Sinai-Trieman, Irit Krause
BACKGROUND: The incidence of post-infectious glomerulonephritis (PIGN) has decreased over the last decades. As a result, recent epidemiological data from industrialized countries are scarce. OBJECTIVES: To evaluate patterns of PIGN in children and detect possible predictors of disease severity. METHODS: We collected clinical and laboratory data of patients with PIGN admitted to Schneider Children's Medical Center during 1994-2011. Diagnostic criteria included presence of hematuria with/without other features of nephritic syndrome along with hypocomplementemia and/or microbiological/serological evidence of streptococcal infection...
June 2016: Israel Medical Association Journal: IMAJ
https://www.readbyqxmd.com/read/27464767/renal-thrombotic-microangiopathy-in-proliferative-lupus-nephritis-risk-factors-and-clinical-outcomes-a-case-control-study
#15
Ana Barrera-Vargas, Rodrigo Rosado-Canto, Javier Merayo-Chalico, José M Arreola-Guerra, Juan M Mejía-Vilet, Ricardo Correa-Rotter, Diana Gómez-Martín, Jorge Alcocer-Varela
BACKGROUND: Renal thrombotic microangiopathy (TMA) may be associated with lupus nephritis. Its relationship to other disease factors and its specific effect on prognosis are not precisely known. Evidence regarding these aspects is controversial, and information focusing on kidney-limited TMA in systemic lupus erythematosus (SLE) patients is scarce. OBJECTIVES: The aims of this study were to identify risk factors for renal TMA in patients with lupus nephritis and to determine its impact on clinical outcomes...
August 2016: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
https://www.readbyqxmd.com/read/27423476/toll-like-receptor-activation-in-the-pathogenesis-of-lupus-nephritis
#16
Georg Lorenz, Maciej Lech, Hans-Joachim Anders
The pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis is complex but no longer enigmatic. Much progress has been made to on the polygenetic origin of lupus in identifying gene variants that permit the loss of tolerance against nuclear autoantigens. Along the same line in about 50% of lupus patients additional genetic weaknesses promote immune complex glomerulonephritis and filtration barrier dysfunction. Here we briefly summarize the pathogenesis of SLE with a focus on loss of tolerance and the role of toll-like receptors in the "pseudo"-antiviral immunity concept of systemic lupus...
July 14, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27407135/pro-inflammatory-s100-proteins-are-associated-with-glomerulonephritis-and-anti-dsdna-antibodies-in-systemic-lupus-erythematosus
#17
H Tydén, C Lood, B Gullstrand, A Jönsen, F Ivars, T Leanderson, A A Bengtsson
OBJECTIVES: Systemic lupus erythematosus (SLE) is associated with elevated levels of S100A8/A9, pro-inflammatory proteins mainly secreted by activated polymorphonuclear neutrophils (PMNs). The underlying mechanisms for increased S100A8/A9 levels and their relation to the clinical phenotype have not been carefully investigated. We assessed S100A8/A9 and S100A12 levels in SLE patient sera in relation to disease activity, clinical phenotype, presence of anti-dsDNA antibodies and ability to promote phagocytosis of necrotic cells (NCs) by PMNs...
July 12, 2016: Lupus
https://www.readbyqxmd.com/read/27392463/dual-blockade-of-the-pro-inflammatory-chemokine-ccl2-and-the-homeostatic-chemokine-cxcl12-is-as-effective-as-high-dose-cyclophosphamide-in-murine-proliferative-lupus-nephritis
#18
Satish Kumar Devarapu, Santhosh Kumar Vr, Khader Valli Rupanagudi, Onkar P Kulkarni, Dirk Eulberg, Sven Klussmann, Hans-Joachim Anders
Induction therapy of proliferative lupus nephritis still requires the use of unselective immunosuppressive drugs with significant toxicities. In search of more specific drugs with equal efficacy but fewer side effects we considered blocking pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) and homeostatic chemokine stromal cell-derived factor-1 (SDF-1/CXCL12), which both contribute to the onset and progression of proliferative lupus nephritis yet through different mechanisms. We hypothesized that dual antagonism could be as potent on lupus nephritis as the unselective immunosuppressant cyclophosphamide (CYC)...
August 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27390299/validation-of-systemic-lupus-erythematosus-diagnosis-as-the-primary-cause-of-renal-failure-in-the-united-states-renal-data-systems
#19
Anna Broder, Wenzhu B Mowrey, Peter Izmirly, Karen H Costenbader
BACKGROUND: Using American College of Rheumatology (ACR) and Systemic Lupus (SLE) International Collaborating Clinics (SLICC) criteria for SLE classification as gold standards, we determined sensitivity, specificity, positive and negative predictive values (PPV and NPV) of having SLE denoted as the primary cause of end-stage renal disease (ESRD) in the United States Renal Data Systems (USRDS). METHODS: ESRD patients were identified by ICD9 codes in electronic medical records of one large tertiary care center, Montefiore hospital, from 2006 to 2012...
July 7, 2016: Arthritis Care & Research
https://www.readbyqxmd.com/read/27390112/vitamin-d-deficiency-is-associated-with-endothelial-dysfunction-and-increases-type-1-interferon-gene-expression-in-a-murine-model-of-sle
#20
John A Reynolds, Avi Z Rosenberg, Carolyne K Smith, Jamie C Sergeant, Gillian I Rice, Tracy A Briggs, Ian N Bruce, Mariana J Kaplan
Objective Patients with Systemic Lupus Erythematosus (SLE) have an increased risk of cardiovascular disease (CVD) and impaired endothelial repair. Although vitamin D deficiency is associated with increased CVD risk in the general population, a causal relationship has not been demonstrated. We aimed to determine whether vitamin D deficiency directly modulates endothelial dysfunction and immune responses in a murine model of SLE. Methods Vitamin D deficiency was induced in lupus-prone MRL/lpr mice by dietary restriction for 6 weeks...
July 7, 2016: Arthritis & Rheumatology
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