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BAFF in SLE

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https://www.readbyqxmd.com/read/28992184/immune-complexes-containing-serum-b-cell-activating-factor-and-immunoglobulin-g-correlate-with-disease-activity-in-systemic-lupus-erythematosus
#1
Justa Friebus-Kardash, Leonore Branco, Camillo Ribi, Carlo Chizzolini, Uyen Huynh-Do, Denise Dubler, Pascale Roux-Lombard, Sebastian Dolff, Andreas Kribben, Ute Eisenberger, Marten Trendelenburg
Background: B-cell activating factor belonging to the TNF family (BAFF) is important for the survival of autoreactive B-cells in systemic lupus erythematosus (SLE). However, the association between serum BAFF levels and SLE disease activity is controversial. Independently, autoantibodies targeting BAFF [immunoglobulin G (IgG) anti-BAFF] have also been described in SLE patients and were associated with increased disease activity. The aim of our study was to analyse the relationship between SLE disease manifestations and serum levels of BAFF, IgG anti-BAFF and BAFF-IgG complexes...
August 8, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28844943/the-unknown-aspect-of-baff-inducing-il-35-production-by-a-cd5-cd1d-hi-fc%C3%AE-riib-hi-regulatory-b-cell-subset-in-lupus
#2
Yamin Zhang, Jun Li, Nuoya Zhou, Yi Zhang, Min Wu, Jian Xu, Chen Shen, Xiangjie An, Guanxin Shen, Ming Yang, Chun Zhang, Juan Tao
IL-35 is a critical immunosuppressive cytokine and plays an important role in various autoimmune diseases. The purpose of this study was to determine whether BAFF, a key pathogenic factor in SLE, also a dichotomous regulator for B cell immune responses, has an effect on IL-35-producing regulatory B cells and its underlying mechanisms in lupus. We found that exogenous BAFF could induce IL-35 production by splenic B cells from MRL-Fas(lpr/lpr) mice. BAFF-induced IL-35-producing B cells were mainly from MZ B cell subset and exhibited a CD5(+)CD1d(hi)FcγRIIb(hi) phenotype...
August 24, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28745239/therapeutic-interventions-of-tissue-specific-autoimmune-onset-in-systemic-lupus-erythematosus
#3
Subhajit Dasgupta
Systemic lupus erythematosus (SLE) is a female predominant autoimmune disease. The onset of SLE has been found to affect kidney, bone, cardiovascular and central nervous system. Auto activation of B cells and T helper cells together are known to develop self-reactive immune responses in SLE. The therapy still includes corticosteroids to prevent allergic manifestations and inflammatory immune responses. Recent observations suggested that, mycophenolate mofetil and cyclophosphamide treatment in combination with corticosteroids have benefit to control disease manifestations...
July 25, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28683581/reduction-of-cd19-autoimmunity-marker-on-b-cells-of-paediatric-sle-patients-through-repressing-pu-1-tnf-%C3%AE-baff-axis-pathway-by-mir-155
#4
H R Aboelenein, M T Hamza, H Marzouk, R A Youness, M Rahmoon, S Salah, A I Abdelaziz
microRNA-155 (miR-155) is implicated in regulating B-cell activation and survival that is important in systemic lupus erythematosus (SLE) pathogenesis. PU.1, a target for miR-155, is a crucial regulator of B-cell development and enhances Tumour-Necrosis-factor-alpha (TNF-α) expression. TNF-α induces the expression of B-cell-activating-factor (BAFF). BAFF is reported to increase the expression of the autoimmunity marker; CD19. This study aimed to investigate the regulation of expression of PU.1 in pediatric-systemic-lupus-erythematosus (pSLE) patients by miR-155, and hence evaluate its impact on TNF-α/BAFF/CD19 signalling pathway...
July 7, 2017: Growth Factors
https://www.readbyqxmd.com/read/28659046/renal-tubular-epithelial-cell-derived-baff-expression-mediates-kidney-damage-and-correlates-with-activity-of-proliferative-lupus-nephritis-in-mouse-and-men
#5
A Schwarting, M Relle, M Meineck, B Föhr, K Triantafyllias, A Weinmann, W Roth, J Weinmann-Menke
B-cell activating factor of the tumour necrosis factor family (BAFF) is a cytokine, mainly produced by hematopoietic cells (e.g. monocytes/macrophages, dendritic cells), indispensable for B-cell maturation. The BLISS studies have demonstrated that blocking BAFF by the human monoclonal antibody belimumab is a valuable therapeutic approach in patients with clinically and serologically active systemic lupus erythematosus (SLE). However, the defined sources of BAFF, which contributes to SLE, are still unclear. Recent findings show that BAFF expression is not restricted to myeloid cells...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28485798/immune-complexes-induce-tnf-%C3%AE-and-baff-production-from-u937-cells-by-hmgb1-and-rage
#6
X-J Gao, Y-Y Qu, X-W Liu, M Zhu, C-Y Ma, Y-L Jiao, B Cui, Z-J Chen, Y-R Zhao
OBJECTIVE: This study investigated the effects of immune complexes (ICs) on tumor necrosis factor α (TNF-α) and B cell-activating factor (BAFF) production from U937 cells and further explored the mechanism. MATERIALS AND METHODS: U937 cells were incubated with necrosis supernatant or systemic lupus erythematosus (SLE) sera alone, or their combination. The expression of TNF-α and BAFF was determined by Real-time polymerase chain reaction and enzyme-linked immunosorbent assay...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28463395/clinical-relevance-of-circulating-anti-ena-and-anti-dsdna-secreting-cells-from-sle-patients-and-their-dependence-on-stat-3-activation
#7
Raquel de la Varga Martínez, Beatriz Rodríguez-Bayona, Gustavo A Añez, Fermín Medina Varo, José J Pérez Venegas, José A Brieva, Carmen Rodríguez
Disturbances of plasma cell homeostasis and auto-antibody production are hallmarks of systemic lupus erythematosus. The aim of this study was to explore the presence of circulating anti-ENA and anti-dsDNA antibody-secreting cells, to determine their dependence on plasma cell-niche cytokines and to analyze their clinical value. The study was performed in SLE patients with serum anti-ENA and/or anti-dsDNA antibodies (n = 57). Enriched B-cell fractions and sorted antibody-secreting cells (CD19(low) CD38(high) ) were obtained from blood...
July 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28445677/overexpression-of-the-cytokine-baff-and-autoimmunity-risk
#8
Maristella Steri, Valeria Orrù, M Laura Idda, Maristella Pitzalis, Mauro Pala, Ilenia Zara, Carlo Sidore, Valeria Faà, Matteo Floris, Manila Deiana, Isadora Asunis, Eleonora Porcu, Antonella Mulas, Maria G Piras, Monia Lobina, Sandra Lai, Mara Marongiu, Valentina Serra, Michele Marongiu, Gabriella Sole, Fabio Busonero, Andrea Maschio, Roberto Cusano, Gianmauro Cuccuru, Francesca Deidda, Fausto Poddie, Gabriele Farina, Mariano Dei, Francesca Virdis, Stefania Olla, Maria A Satta, Mario Pani, Alessandro Delitala, Eleonora Cocco, Jessica Frau, Giancarlo Coghe, Lorena Lorefice, Giuseppe Fenu, Paola Ferrigno, Maria Ban, Nadia Barizzone, Maurizio Leone, Franca R Guerini, Matteo Piga, Davide Firinu, Ingrid Kockum, Izaura Lima Bomfim, Tomas Olsson, Lars Alfredsson, Ana Suarez, Patricia E Carreira, Maria J Castillo-Palma, Joseph H Marcus, Mauro Congia, Andrea Angius, Maurizio Melis, Antonio Gonzalez, Marta E Alarcón Riquelme, Berta M da Silva, Maurizio Marchini, Maria G Danieli, Stefano Del Giacco, Alessandro Mathieu, Antonello Pani, Stephen B Montgomery, Giulio Rosati, Jan Hillert, Stephen Sawcer, Sandra D'Alfonso, John A Todd, John Novembre, Gonçalo R Abecasis, Michael B Whalen, Maria G Marrosu, Alessandra Meloni, Serena Sanna, Myriam Gorospe, David Schlessinger, Edoardo Fiorillo, Magdalena Zoledziewska, Francesco Cucca
BACKGROUND: Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways...
April 27, 2017: New England Journal of Medicine
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
#9
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/28388832/associations-of-b-cell-activating-factor-baff-and-anti-baff-autoantibodies-with-disease-activity-in-multi-ethnic-asian-systemic-lupus-erythematosus-patients-in-singapore
#10
H S Howe, B Y H Thong, K O Kong, H H Chng, T Y Lian, F L Chia, K S S Tay, T C Lau, W G Law, E T Koh, B P Leung
To measure the levels of B cell-activating factor (BAFF) and endogenous anti-BAFF autoantibodies in a cohort of multi-ethnic Asian systemic lupus erythematosus (SLE) patients in Singapore, to determine their correlation with disease activity. Serum samples from 121 SLE patients and 24 age- and sex-matched healthy controls were assayed for BAFF and anti-BAFF immunoglobulin (Ig)G antibody levels by enzyme-linked immunosorbent assay (ELISA). The lowest reliable detection limit for anti-BAFF-IgG antibody levels was defined as 2 standard deviations (s...
September 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28383107/a-mouse-model-of-systemic-lupus-erythematosus-responds-better-to-soluble-taci-than-to-soluble-baffr-correlating-with-depletion-of-plasma-cells
#11
Philipp Haselmayer, Michele Vigolo, Josquin Nys, Pascal Schneider, Henry Hess
The TNF family cytokines B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) support plasma cell survival. It is known that inhibitors of BAFF only (BAFFR-Fc) or BAFF and APRIL (TACI-Fc) administered early enough in an NZB/NZW F1 mouse model of systemic lupus erythematosus (SLE) ameliorate clinical outcomes, pointing to a pathogenic role of BAFF. In the present study, TACI-Fc administrated at a later stage of disease, after onset of autoimmunity, decreased the number of bone marrow plasma cells and slowed down further formation of autoantibodies...
June 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28331294/spotlight-on-blisibimod-and-its-potential-in-the-treatment-of-systemic-lupus-erythematosus-evidence-to-date
#12
REVIEW
Aleksander Lenert, Timothy B Niewold, Petar Lenert
B cells in general and BAFF (B cell activating factor of the tumor necrosis factor [TNF] family) in particular have been primary targets of recent clinical trials in systemic lupus erythematosus (SLE). In 2011, belimumab, a monoclonal antibody against BAFF, became the first biologic agent approved for the treatment of SLE. Follow-up studies have shown excellent long-term safety and tolerability of belimumab. In this review, we critically analyze blisibimod, a novel BAFF-neutralizing agent. In contrast to belimumab that only blocks soluble BAFF trimer but not soluble 60-mer or membrane BAFF, blisibimod blocks with high affinity all three forms of BAFF...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28215100/targeting-baff-and-april-in-systemic-lupus-erythematosus-and-other-antibody-associated-diseases
#13
Eileen Samy, Stephen Wax, Bertrand Huard, Henry Hess, Pascal Schneider
The B cell-stimulating molecules, BAFF (B cell activating factor) and APRIL (a proliferation-inducing ligand), are critical factors in the maintenance of the B cell pool and humoral immunity. In addition, BAFF and APRIL are involved in the pathogenesis of a number of human autoimmune diseases, with elevated levels of these cytokines detected in the sera of patients with systemic lupus erythematosus (SLE), IgA nephropathy, Sjögren's syndrome, and rheumatoid arthritis. As such, both molecules are rational targets for new therapies in B cell-driven autoimmune diseases, and several inhibitors of BAFF or BAFF and APRIL together have been investigated in clinical trials...
January 2, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28164726/inhibition-of-b-cell-activating-factor-baff-in-the-management-of-systemic-lupus-erythematosus-sle
#14
William Stohl
The anti-BAFF monoclonal antibody, belimumab, was approved 5+ years ago by the US Food and Drug Administration for the treatment of adult SLE patients. Although BAFF is now a proven therapeutic target in SLE, the limited clinical efficacy both in the clinical trials setting and in 'real-life' experience begs for further therapeutic improvement. Areas covered: In addition to belimumab, three other BAFF antagonists (atacicept, blisibimod, tabalumab) that biologically differ from belimumab are being or have been evaluated in SLE late-stage clinical trials...
June 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28089248/triggering-receptor-expressed-on-myeloid-cells-1-trem-1-deficiency-augments-baff-production-to-promote-lupus-progression
#15
Chi-Jui Liu, Chang-Youh Tsai, Ssu-Hsuan Chiang, Shye-Jye Tang, Nien-Jung Chen, Tak Wah Mak, Guang-Huan Sun, Kuang-Hui Sun
Sensing of nucleic acids by pattern recognition receptors is the key for the initiation and development of systemic lupus erythematosus (SLE). Triggering receptor expressed on myeloid cells-1 (TREM-1) is a novel innate immune receptor, which can amplify Toll-like receptor (TLR)-induced inflammatory responses. Although patients with lupus exhibit increased serum levels of soluble TREM-1 (sTREM-1), the role of TREM-1 in SLE remains unknown. In current study, we found serum sTREM-1 levels were significantly increased in lupus patients and positively correlated with disease activity...
January 11, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27923569/gender-differences-of-b-cell-signature-related-to-estrogen-induced-ifi44l-baff-in-systemic-lupus-erythematosus
#16
Hongye Fan, Guangfeng Zhao, Deshan Ren, Fei Liu, Guanjun Dong, Yayi Hou
Systemic lupus erythematosus (SLE) possesses a gender-dependent incidence characterized by a male/female ratio 1:9. B-cell, a vital part of the immune system, plays an important role in pathogenesis of SLE. Thus, we hypothesize that gender differences of B cells may exist in SLE and relate to the onset and the progression of SLE. Here, we showed that the genes expression pattern is similar between healthy female and male. However, SLE female and SLE male showed more upregulated genes, in which the trendline of SLE male is higher than that of SLE female...
December 5, 2016: Immunology Letters
https://www.readbyqxmd.com/read/27903029/-lupus-erythematosus-update-2016
#17
REVIEW
Martin Aringer, Reinhard Edmund Voll
Meanwhile, five years have passed since the approval of the anti-BAFF antibody belimumab as a first biological for SLE, but no further SLE drug candidate is even close to approval. There are still no clinical trial data available for the use of new oral anticoagulants in antiphospholipid syndrome. In spite of convincing evidence for the use of mycophenolate mofetil (MMF) in lupus nephritis, the German "Gemeinsame Bundesausschuss" (GBA) has not yet decided on its reimbursement. However, several of the ongoing clinical trials have potential to lead to important advances in SLE treatment in the future...
November 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27723281/gene-expression-and-pharmacodynamic-changes-in-1-760-systemic-lupus-erythematosus-patients-from-two-phase-iii-trials-of-baff-blockade-with-tabalumab
#18
RANDOMIZED CONTROLLED TRIAL
Robert W Hoffman, Joan T Merrill, Marta M E Alarcón-Riquelme, Michelle Petri, Ernst R Dow, Eric Nantz, Laura K Nisenbaum, Krista M Schroeder, Wendy J Komocsar, Narayanan B Perumal, Matthew D Linnik, David C Airey, Yushi Liu, Guilherme V Rocha, Richard E Higgs
OBJECTIVE: To characterize baseline gene expression and pharmacodynamically induced changes in whole blood gene expression in 1,760 systemic lupus erythematosus (SLE) patients from 2 phase III, 52-week, randomized, placebo-controlled, double-blind studies in which patients were treated with the BAFF-blocking IgG4 monoclonal antibody tabalumab. METHODS: Patient samples were obtained from SLE patients from the ILLUMINATE-1 and ILLUMINATE-2 studies, and control samples were obtained from healthy donors...
March 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27592380/from-old-concerns-to-new-advances-and-personalized-medicine-in-lupus-the-end-of-the-tunnel-is-approaching
#19
EDITORIAL
Andrea Doria, M Eric Gershwin, Carlo Selmi
The significant decrease in mortality rates worldwide, the increased proportion of patients achieving a durable remission, and the recent approval of a new drug after several decades are encouraging advances in the tangled history of systemic lupus erythematosus (SLE). However, when data are observed more closely, the research findings on disease pathogenesis and targeted treatments have been quite misleading, as illustrated by the central role of B cells but the missed endpoints in rituximab clinical trials which are burdened by the wide variability of SLE manifestations or the ethnic determinants of disease severity...
November 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27587201/a-review-of-clinical-trials-of-belimumab-in-the-management-of-systemic-lupus-erythematosus
#20
Alexis Garcia, Juan B De Sanctis
There have been few changes over the last 50 years in the treatment of Systemic lupus erythematosus (SLE), using non-specific anti-inflammatory agents such as: nonsteroidal anti-inflammatory drugs along with the immune cell modulating agent hydroxychloroquine for mild disease, and broad spectrum immunosuppressants plus antiinflammatories such as corticosteroids, azathioprine, cyclophosphamide, or mycophenolate during flares or severe disease with organ involvement. In some patients, the response is inadequate and side effects appear from mild unpleasant up to severe toxicity...
2016: Current Pharmaceutical Design
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