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systemic lupus , glomerulonephritis

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https://www.readbyqxmd.com/read/28405610/btk-specific-inhibition-blocks-pathogenic-plasma-cell-signatures-and-myeloid-cell-associated-damage-in-ifn%C3%AE-driven-lupus-nephritis
#1
Arna Katewa, Yugang Wang, Jason A Hackney, Tao Huang, Eric Suto, Nandhini Ramamoorthi, Cary D Austin, Meire Bremer, Jacob Zhi Chen, James J Crawford, Kevin S Currie, Peter Blomgren, Jason DeVoss, Julie A DiPaolo, Jonathan Hau, Adam Johnson, Justin Lesch, Laura E DeForge, Zhonghua Lin, Marya Liimatta, Joseph W Lubach, Sami McVay, Zora Modrusan, Allen Nguyen, Chungkee Poon, Jianyong Wang, Lichuan Liu, Wyne P Lee, Harvey Wong, Wendy B Young, Michael J Townsend, Karin Reif
Systemic lupus erythematosus (SLE) is often associated with exaggerated B cell activation promoting plasma cell generation, immune-complex deposition in the kidney, renal infiltration of myeloid cells, and glomerular nephritis. Type-I IFNs amplify these autoimmune processes and promote severe disease. Bruton's tyrosine kinase (Btk) inhibitors are considered novel therapies for SLE. We describe the characterization of a highly selective reversible Btk inhibitor, G-744. G-744 is efficacious, and superior to blocking BAFF and Syk, in ameliorating severe lupus nephritis in both spontaneous and IFNα-accelerated lupus in NZB/W_F1 mice in therapeutic regimens...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28391340/targeting-the-tyrosine-kinase-signalling-pathways-for-treatment-of-immune-mediated-glomerulonephritis-from-bench-to-bedside-and-beyond
#2
Terry King-Wing Ma, Stephen P McAdoo, Frederick Wai Keung Tam
Glomerulonephritis (GN) affects patients of all ages and is an important cause of morbidity and mortality. Non-selective immunosuppressive drugs have been used in immune-mediated GN but often result in systemic side effects and occasionally fatal infective complications. There is increasing evidence from both preclinical and clinical studies that abnormal activation of receptor and non-receptor tyrosine kinase signalling pathways are implicated in the pathogenesis of immune-mediated GN. Activation of spleen tyrosine kinase (SYK), Bruton's tyrosine kinase (BTK), platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR) and discoidin domain receptor 1 (DDR1) have been demonstrated in anti-GBM disease...
January 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28356164/excessive-activation-of-the-tlr9-tgf-%C3%AE-1-pdgf-b-pathway-in-the-peripheral-blood-of-patients-with-systemic-lupus-erythematosus
#3
Yi Yuan, Mingyue Yang, Kuo Wang, Jing Sun, Lili Song, Xue Diao, Zhenyu Jiang, Genhong Cheng, Xiaosong Wang
BACKGROUND: Our aim is to study the existence of the TLR9/TGF-β1/PDGF-B pathway in healthy humans and patients with systemic lupus erythematosus (SLE), and to explore its possible involvement in the pathogenesis of lupus nephritis (LN). METHODS: Protein levels of the cytokines were detected by ELISA. mRNA levels of the cytokines were analyzed by real-time PCR. MTT assay was used to test the proliferation of mesangial cells under different treatments. RESULTS: Compared to healthy controls (N Control = 56), levels of Toll-like receptor (TLR)9, transforming growth factor (TGF)-β1, and platelet-derived growth factor B (PDGF-B) were increased significantly in the peripheral blood of SLE patients (N SLE = 112)...
March 29, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28341889/complement-regulation-and-kidney-diseases-recent-knowledge-of-the-double-edged-roles-of-complement-activation-in-nephrology
#4
REVIEW
Masashi Mizuno, Yasuhiro Suzuki, Yasuhiko Ito
The complement activation system plays important roles to maintain homeostasis in the host and to fight foreign invaders to protect the host. Therefore, the complement system is considered a core part of innate immunity which also cross-talks to acquired immunity. In the history of nephrology, the complement system is familiar to us, because complement protein or fragment deposition, including C3, C4, C1q, and/or C4d, is routinely estimated by immunohistochemistry to diagnose renal pathologies. The relationships between pathological mechanisms and complement activation have been investigated for renal diseases such as post-infectious glomerulonephritis, lupus nephritis, and primary membranoproliferative glomerulonephritis, which are usually accompanied by hypocomplementemia...
March 24, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28340077/idiopathic-non-lupus-full-house-nephropathy-is-associated-with-poor-renal-outcome
#5
Emilie C Rijnink, Y K Onno Teng, Tineke Kraaij, Ron Wolterbeek, Jan A Bruijn, Ingeborg M Bajema
Background.: Full-house immunofluorescence in combination with various histopathologic lesions in the renal biopsies of patients without overt systemic lupus erythematosus (SLE) poses a diagnostic challenge. In this setting, the biopsy findings are sometimes termed non-lupus 'full-house nephropathy' (FHN). It is presently unknown whether idiopathic non-lupus FHN is clinicopathologically and prognostically distinct from lupus FHN. Methods.: We included non-lupus FHN patients and lupus FHN controls (four or more American College of Rheumatology or Systemic Lupus International Collaborating Clinics criteria) who were biopsied between 1968 and 2014 at the Leiden University Medical Centre...
April 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28320458/b-cell-epitope-of-human-cytomegalovirus-phosphoprotein-65-hcmv-pp65-induced-anti-dsdna-antibody-in-balb-c-mice
#6
Ao HoHsieh, Chin Man Wang, Yeong-Jian Jan Wu, Albert Chen, Ming-I Chang, Ji-Yih Chen
BACKGROUND: HCMV phosphoprotein 65 (HCMVpp65) is a putative immunogen that acts as an accelerator, inducing autoantibody and exacerbating autoimmune response in susceptible animals. The immunity to pp65336-439 instigates autoimmunity, suggesting that pp65336-439 contains crucial B cell epitope(s) for the development of nephritis. This study narrowed down the target epitope to pp65422-439 for immunization of BALB/c mice and mapping of B cell epitope. METHODS: The target epitope pp65422-439 reactivity and B cell epitope mapping was examined in serum from pp65422-439-immunized mice and patients with systemic lupus erythematosus (SLE)...
March 21, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28300543/antibodies-against-monomeric-c-reactive-protein-a-promising-biomarker-of-lupus-nephritis
#7
Katarzyna Jakuszko, Magdalena Krajewska, Katarzyna Kościelska-Kasprzak, Marta Myszka, Agata Sebastian, Katarzyna Gniewek, Piotr Wiland, Marian Klinger
OBJECTIVE AND AIM: A significant incidence of systemic lupus erythematosus (SLE), the severity of lupus nephritis and varying responses to treatment rationalize the search for novel biomarkers of disease activity. The aim of the study was to assess whether antibodies against monomeric C reactive protein (anti-mCRP) are associated with the presence of lupus nephritis, correlate with disease activity, and whether they can serve to evaluate a response to treatment. METHODS: The study involved 74 patients with lupus nephritis, 29 patients with systemic lupus without renal involvement and 31 patients with primary glomerulonephritis; the control group included 31 healthy volunteers...
March 11, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28277147/renal-biopsy-in-patients-with-systemic-lupus-erythematosus-not-just-lupus-glomerulonephritis
#8
David N Howell
Kidney biopsy is a mainstay in the diagnosis and management of renal disease in patients with systemic lupus erythematosus. Though biopsies from patients with lupus typically show various forms of immune complex glomerulonephritis, other pathologies are occasionally encountered, including unusual lupus-related nephropathies, other forms of autoimmune disease, and occasional renal disorders without any direct connection with lupus or autoimmunity. Electron microscopy is a powerful tool for detecting and classifying these unusual conditions, which frequently have important therapeutic and prognostic implications...
March 2017: Ultrastructural Pathology
https://www.readbyqxmd.com/read/28267197/taci-dependent-april-signaling-maintains-autoreactive-b-cells-in-a-mouse-model-of-systemic-lupus-erythematosus
#9
Ngoc Lan Tran, Pascal Schneider, Marie-Laure Santiago-Raber
Autoantibodies contribute to the development of Systemic Lupus Erythematosus (SLE). APRIL (a proliferation-inducing ligand), a member of the TNF superfamily, regulates plasma-cell survival and binds to TACI (transmembrane activator CAML interactor) and BCMA (B cell maturation antigen). We previously showed that APRIL blockade delayed disease onset in lupus-prone mice. In order to evaluate the role of APRIL receptors in the development of SLE, APRIL, TACI, BCMA or double TACI.BCMA null mutations were introduced into the Nba2...
March 7, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28219887/disruption-of-pathogenic-cellular-networks-by-il-21-blockade-leads-to-disease-amelioration-in-murine-lupus
#10
Jin-Young Choi, Abhinav Seth, Michael Kashgarian, Sonia Terrillon, Emma Fung, Lili Huang, Li Chun Wang, Joe Craft
Systemic lupus erythematosus (lupus) is characterized by autoantibody-mediated organ injury. Follicular Th (Tfh) cells orchestrate physiological germinal center (GC) B cell responses, whereas in lupus they promote aberrant GC responses with autoreactive memory B cell development and plasma cell-derived autoantibody production. IL-21, a Tfh cell-derived cytokine, provides instructional cues for GC B cell maturation, with disruption of IL-21 signaling representing a potential therapeutic strategy for autoantibody-driven diseases such as systemic lupus erythematosus...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28207635/kidney-transplantation-rates-across-glomerulonephritis-subtypes-in-the-united-states
#11
Michelle M O'Shaughnessy, Sai Liu, Maria E Montez-Rath, Richard A Lafayette, Wolfgang C Winkelmayer
BACKGROUND: Whether kidney transplantation rates differ by glomerulonephritis (GN) subtype remains largely unknown. METHODS: Using the US Renal Data System, we identified all adult patients with ESRD attributed to 1 of 6 GN subtypes who initiated dialysis in the US (1996-2013). Patients with diabetic nephropathy (DN) and autosomal-dominant polycystic kidney disease (ADPKD) served as "external" non-GN comparators. Using Cox proportional hazards regression, with death considered a competing risk, we estimated hazard ratios [HRs (95% confidence intervals)] for first kidney transplantation, controlling for year, demographics, comorbidities, socioeconomic factors, and Organ Procurement Organization (OPO)...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28176476/recurrent-atypical-haemolytic-uraemic-syndrome-post-kidney-transplant-due-to-a-cd46-mutation-in-the-setting-of-smarcal1-mediated-inherited-kidney-disease
#12
REVIEW
Samuel Chan, Andrew J Mallett, Chirag Patel, Ross S Francis, David W Johnson, David W Mudge, Nicole M Isbel
Disorders in the regulation of the alternate complement pathway often result in complement-mediated damage to the microvascular endothelium and can be associated with both glomerulonephritis and atypical haemolytic uraemic syndrome. Inherited defects in complement regulatory genes or autoantibodies against complement regulatory proteins are predictive of the severity of the disease and the risk of recurrence post kidney transplantation. Heterozygous mutations in CD46, which codes for a transmembrane cofactor glycoprotein membrane cofactor protein, usually have a lower incidence of end-stage kidney disease and decreased risk of recurrent disease post transplant, as wild-type membrane cofactor protein is present in the transplanted kidney...
February 2017: Nephrology
https://www.readbyqxmd.com/read/28133935/post-transplant-immune-complex-nephritis-in-a-patient-with-systemic-lupus-erythematosus-associated-with-anca-vasculitis
#13
Carlos Sanchez, Alejandra Rebolledo, Junior Gahona, Mauricio Rojas, Raquel Jiménez, Aurora Bojórquez
Nearly 20% of SLE corresponds to the pediatric population, and 75% of them have kidney involvement representing an important etiology of chronic kidney disease. A correlation between SLE and ANCA-associated vasculitis has been identified as an overlapping syndrome. Kidney allograft recurrence is rare in SLE when disease control is achieved and with nowadays immunosuppression treatment. Histologic transformation is unusual, especially when there are negative serologic markers and no immune complex deposition reported in native kidneys...
May 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28130617/prolactin-has-a-pathogenic-role-in-systemic-lupus-erythematosus
#14
Luis J Jara, Gabriela Medina, Miguel A Saavedra, Olga Vera-Lastra, Honorio Torres-Aguilar, Carmen Navarro, Monica Vazquez Del Mercado, Luis R Espinoza
Prolactin, a 23-kDa peptide hormone, is produced by the anterior pituitary gland and extrapituitary sites including the immune cells. Prolactin (PRL) participates in innate and adaptive immune response. PRL stimulates the immune cells by binding to receptor (PRL-R). Binding of PRL to its receptor activates the Janus kinase-signal transducer (JAK-STAT). Activation of these cascades results in endpoints such as immunoestimulator and immunosupressor action. Prolactin belongs to the network of immune-neuroendocrine interaction...
January 28, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28123335/posterior-reversible-encephalopathy-syndrome-in-children-a-case-series
#15
Serhat Emeksiz, Nurettin Onur Kutlu, Hüseyin Çaksen, Gülsüm Alkan, Hülya Şeker Yıkmaz, Hüseyin Tokgöz
Posterior reversible encephalopathy syndrome is characterized by hypertension, seizure, headache, clouding of consciousness, and visual disturbance, and is diagnosed in the presence of typical lesions on magnetic resonance imaging. We retrospectively evaluated five patients who were diagnosed as having posterior reversible encephalopathy syndrome and followed up in Meram Medical Faculty, Pediatric Intensive Care and Hematology wards, between January 2010 and January 2014. We reviewed the demographic and clinical data, and neuroimaging findings...
December 2016: Türk Pediatri Arşivi
https://www.readbyqxmd.com/read/28116572/uch-l1-expressed-by-podocytes-a-potentially-therapeutic-target-for-lupus-nephritis
#16
Ji-Hong Cui, Xin Xie
Systemic lupus erythematosus (SLE) is a multisystem disease affecting many organs, and the most severe complication is lupus nephritis. Podocyte injury and loss play vital roles in the pathogenesis of lupus nephritis. Studies have shown that ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is involved in the pathogenesis and progression of many diseases, such as neurodegenerative disorders, cancers, and diabetes. Recently, numerous studies have indicated that UCH-L1 was upregulated in the podocytes in immune complex-mediated glomerulonephritis...
April 2017: Inflammation
https://www.readbyqxmd.com/read/27994909/assessment-of-ten-year-long-results-of-kidney-biopsies-performed-on-children-in-the-thrace-region-of-turkey
#17
Neşe Özkayın, Gökçe Çıplak, Ufuk Usta, Hakan Gençhellaç, Osman Temizöz
BACKGROUND: Many children with kidney diseases can be diagnosed and treated without a biopsy. However, biopsy is a valuable method for the diagnostic and prognostic evaluation of children with kidney diseases. AIMS: To evaluate the clinical and pathological profiles of the kidney biopsies in our department to provide epidemiological data for clinical practice. STUDY DESIGN: Retrospective cross-sectional study. METHODS: Kidney biopsies and patient's charts in pediatric patients performed between May 2005 and February 2015 at the Pediatric Nephrology Department, Trakya University School of Medicine were assessed retrospectively...
November 2016: Balkan Medical Journal
https://www.readbyqxmd.com/read/27994272/alveolar-hemorrhage-as-the-initial-presentation-of-systemic-lupus-erythematosus
#18
Bruna A de Holanda, Isabela G Menna Barreto, Isadora S Gomes de Araujo, Daniel B de Araujo
Alveolar hemorrhage (AH) is a rare syndrome that can often occur in autoimmune diseases, blood clotting disorders, infection or by acute inhalation injury, presenting rapid evolution and high mortality, especially with late diagnosis and treatment. Among the autoimmune diseases, there are reported cases in patients with primary antiphospholipid syndrome (PAPS), vasculitis and systemic lupus erythematosus (SLE). An early diagnosis is an essential tool in the successful management of this complication, requiring aggressive treatment based on vigorous immunosuppression and broad-spectrum antibiotic...
2016: Reumatologia
https://www.readbyqxmd.com/read/27992697/vista-deficiency-accelerates-the-development-of-fatal-murine-lupus-nephritis
#19
Sabrina Ceeraz, Petra A Sergent, Sean F Plummer, Alan R Schned, Dov Pechenick, Christopher M Burns, Randolph J Noelle
OBJECTIVE: The targeting of negative checkpoint regulators as a means of augmenting antitumor immune responses is now an increasingly used and remarkably effective approach to the treatment of several human malignancies. The negative checkpoint regulator VISTA (V-domain Ig-containing suppressor of T cell activation; also known as programmed death 1 homolog or as death domain 1α) suppresses T cell responses and regulates myeloid activities. We proposed that exploitation of the VISTA pathway is a novel strategy for the treatment of human autoimmune disease, and therefore we undertook this study to determine the impact of VISTA genetic deficiency on lupus development in a lupus-prone mouse strain...
April 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27958636/intrauterine-growth-restriction-in-pregnant-women-after-kidney-transplantation-as-a-marker-of-preeclampsia
#20
Anna Cyganek, Filip Andrzej Dabrowski, Bronislawa Pietrzak, Zoulikha Jabiry-Zieniewicz, Barbara Grzechocinska, Anna Madej, Miroslaw Wielgos
OBJECTIVES: Delayed motherhood is associated with an increasing number of comorbidities such as glomerulonephritis, systemic lupus erythematosus, and diabetic nephropathy. Women after renal transplant belong to the group of patients who require a highly individualized approach to treatment and diagnosis. The aim of the study was to validate the commonly used diagnostic criteria for preeclampsia which seem to be irrelevant in patients with chronic renal insufficiency. MATERIAL AND METHODS: The course of pregnancy and delivery were retrospectively analyzed in 48 renal transplant patients...
2016: Ginekologia Polska
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