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https://www.readbyqxmd.com/read/28331294/spotlight-on-blisibimod-and-its-potential-in-the-treatment-of-systemic-lupus-erythematosus-evidence-to-date
#1
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/28323891/characterization-of-baff-and-april-subfamily-receptors-in-rainbow-trout-oncorhynchus-mykiss-potential-role-of-the-baff-april-axis-in-the-pathogenesis-of-proliferative-kidney-disease
#2
Aitor G Granja, Jason W Holland, Jaime Pignatelli, Christopher J Secombes, Carolina Tafalla
Proliferative kidney disease (PKD) is a parasitic infection of salmonid fish characterized by hyper-secretion of immunoglobulins in response to the presence of the myxozoan parasite, Tetracapsuloides bryosalmonae. In this context, we hypothesized that the BAFF/APRIL axis, known to play a major role in B cell differentiation and survival in mammals, could be affected by the parasite and consequently be involved in the apparent shift in normal B cell activity. To regulate B cell activity, BAFF and APRIL bind to transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA), whereas BAFF also binds to BAFF receptor (BAFF-R)...
2017: PloS One
https://www.readbyqxmd.com/read/28302579/the-baff-april-axis-plays-an-important-role-in-virus-induced-peritoneal-responses-in-rainbow-trout
#3
Irene Soleto, Beatriz Abós, Rosario Castro, Lucia González, Carolina Tafalla, Aitor G Granja
IgM(+) B cells have been recently demonstrated to be key regulators of peritoneal inflammation in teleost, as a large number of them occupy the peritoneal cavity after 48 h of antigenic stimulation. Despite this, the number of studies addressing the mechanism through which this cell population expands and differentiates in response to stimuli has been scarcely addressed. Because the BAFF/APRIL axis is known to play a major role in B cell survival and differentiation in mammals, we hypothesized that it could be affected in the peritoneal cavity in response to an inflammatory stimulus...
March 14, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28300280/rapamycin-attenuates-baff-extended-proliferation-and-survival-via-disruption-of-mtorc1-2-signaling-in-normal-and-neoplastic-b-lymphoid-cells
#4
Qingyu Zeng, Shanshan Qin, Hai Zhang, Beibei Liu, Jiamin Qin, Xiaoxue Wang, Ruijie Zhang, Chunxiao Liu, Xiaoqing Dong, Shuangquan Zhang, Shile Huang, Long Chen
B cell activating factor from the TNF family (BAFF) stimulates B-cell proliferation and survival, but excessive BAFF promotes the development of aggressive B cells leading to malignant and autoimmune diseases. Recently, we have reported that rapamycin, a macrocyclic lactone, attenuates human soluble BAFF (hsBAFF)-stimulated B-cell proliferation/survival by suppressing mTOR-mediated PP2A-Erk1/2 signaling pathway. Here, we show that the inhibitory effect of rapamycin on hsBAFF-promoted B cell proliferation/survival is also related to blocking hsBAFF-stimulated phosphorylation of Akt, S6K1 and 4E-BP1, as well as expression of survivin in normal and B-lymphoid (Raji and Daudi) cells...
March 16, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28298648/lupus-nephritis-novel-role-for-baff-in-tertiary-lymphoid-neogenesis
#5
Joanna Collison
No abstract text is available yet for this article.
March 16, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28296027/transitional-b-cells-predominantly-reconstituted-after-a-desensitization-therapy-using-rituximab-before-kidney-transplantation
#6
Masako Ikemiyagi, Toshihito Hirai, Rumi Ishii, Satoshi Miyairi, Masayoshi Okumi, Kazunari Tanabe
The role of B cells in graft rejection and tolerance has aroused great interest. We previously reported that rituximab (RIT) induction prior to kidney transplantation (KTx) reduced the incidence rate of chronic rejection. Here, we performed a cross sectional investigation to determine the characteristics of B cells after RIT induction for KTx. We sampled blood from 29 patients with (N = 16) and without (N = 13) RIT induction 3 to 18 months after KTx. In the RIT group, the majority of repopulating B cells was the transitional type, while memory B cells were scarce...
March 13, 2017: Therapeutic Apheresis and Dialysis
https://www.readbyqxmd.com/read/28289419/cytokine-signatures-in-mucocutaneous-and-ocular-beh%C3%A3-et-s-disease
#7
Giuseppe Lopalco, Orso Maria Lucherini, Antonio Lopalco, Vincenzo Venerito, Claudia Fabiani, Bruno Frediani, Mauro Galeazzi, Giovanni Lapadula, Luca Cantarini, Florenzo Iannone
Behçet's disease (BD) is a multi-systemic inflammatory disorder consisting of recurrent oral aphthosis, genital ulcers, and chronic relapsing bilateral uveitis; however, many other organs may be affected. Several pro-inflammatory cytokines, mainly derived from Th1 and Th17 lymphocytes, seem to be involved in different pathogenic pathways leading to development of the clinical manifestations. On this basis, the primary aim of our study was to compare a core set of pro-inflammatory cytokines between patients with BD and healthy control (HC)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28288328/case-control-exploratory-study-of-cerebrospinal-fluid-chemokines-cytokines-and-lymphocyte-subsets-in-childhood-tourette-syndrome-with-positive-streptococcal-markers
#8
Michael R Pranzatelli, Elizabeth D Tate, Tyler J Allison
A longstanding question is whether neuroinflammation is present in children symptomatic for Tourette syndrome (TS) with positive streptococcal serology and throat cultures. The objective was to directly test for it using modern hypothesis-driven approaches. Profiling studies for 14 immune cell types (flow cytometry), 7 chemokines/cytokines (ELISA), oligoclonal bands, and other immunoglobulins were performed in this IRB-approved study of 5 children with TS and streptococcal markers compared to data from 26 non-inflammatory pediatric neurological controls...
March 10, 2017: Cytokine
https://www.readbyqxmd.com/read/28284352/raised-cerebrospinal-fluid-baff-and-april-levels-in-anti-n-methyl-d-aspartate-receptor-encephalitis-correlation-with-clinical-outcome
#9
Bo Deng, Xiao-Ni Liu, Xiang Li, Xiang Zhang, Chao Quan, Xiang-Jun Chen
In this study, we aimed to assess the levels of B cell activating factor from the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) in cerebrospinal fluid (CSF) of patients with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and determine their correlation with clinical outcome. BAFF and APRIL concentrations in CSF and serum from 40 patients with anti-NMDAR encephalitis and 20 controls were measured by enzyme-linked immunosorbent assay (ELISA). Compared with controls, the levels of both BAFF and APRIL in CSF were significantly increased in patients with anti-NMDAR encephalitis (p<0...
April 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28283566/human-plasmacytoid-dendritic-cells-display-and-shed-b-cell-maturation-antigen-upon-tlr-engagement
#10
Elisabeth Schuh, Andrea Musumeci, Franziska S Thaler, Sarah Laurent, Joachim W Ellwart, Reinhard Hohlfeld, Anne Krug, Edgar Meinl
The BAFF-APRIL system is best known for its control of B cell homeostasis, and it is a target of therapeutic intervention in autoimmune diseases and lymphoma. By analyzing the expression of the three receptors of this system, B cell maturation Ag (BCMA), transmembrane activator and CAML interactor, and BAFF receptor, in sorted human immune cell subsets, we found that BCMA was transcribed in plasmacytoid dendritic cells (pDCs) in both blood and lymphoid tissue. Circulating human pDCs contained BCMA protein without displaying it on the cell surface...
March 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28275260/beyond-tnf-tnf-superfamily-cytokines-as-targets-for-the-treatment-of-rheumatic-diseases
#11
REVIEW
Michael Croft, Richard M Siegel
TNF blockers are highly efficacious at dampening inflammation and reducing symptoms in rheumatic diseases such as rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, and also in nonrheumatic syndromes such as inflammatory bowel disease. As TNF belongs to a superfamily of 19 structurally related proteins that have both proinflammatory and anti-inflammatory activity, reagents that disrupt the interaction between proinflammatory TNF family cytokines and their receptors, or agonize the anti-inflammatory receptors, are being considered for the treatment of rheumatic diseases...
April 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28274776/corrigendum-to-chemokine-cytokine-profiling-after-rituximab-reciprocal-expression-of-bca-1-cxcl13-and-baff-in-childhood-oms-cytokine-53-2011-384-389
#12
Michael R Pranzatelli, Elizabeth D Tate, Anna L Travelstead, Steven J Verhulst
No abstract text is available yet for this article.
March 5, 2017: Cytokine
https://www.readbyqxmd.com/read/28270182/effect-of-fcgr-polymorphism-on-the-occurrence-of-late-onset-neutropenia-and-flare-free-survival-in-rheumatic-patients-treated-with-rituximab
#13
Sofia Ajeganova, Daniel Tesfa, Hans Hägglund, Bengt Fadeel, Inger Vedin, Anna Linda Zignego, Jan Palmblad
BACKGROUND: The causes and mechanisms of late-onset neutropenia (LON) following rituximab treatment in patients with rheumatic diseases are not known. In this study, we aimed to investigate the role of established Fcγ receptor gene (FCGR) polymorphisms and B-cell-activating factor (BAFF) gene promoter polymorphisms for the development of LON and for the efficacy of rituximab in patients with rheumatic diseases. METHODS: A single-center case-control retrospective study was nested in a cohort of 214 consecutive patients with rheumatic diseases treated with rituximab...
March 7, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28260502/selective-binding-baff-april-by-the-in-and-outside-conservative-region-of-bcma
#14
Chang Zheng, Xiaojuan Zhang, Zhen Zhao, Xiaofei Hao, Jing Wei, Jian Sun
B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) play vital roles in the pathogenesis of autoimmune diseases. B cell maturation antigen (BCMA), a receptor of both BAFF and APRIL shows higher affinity for APRIL than for BAFF. In this study, the conserved region of BCMA was divided into two segments BCMA1 (NEYFDSLLHACIPC) and BCMA2 (QLRCSSNTPPLT) with the aim to investigate their contribution to the ligands binding, BCMA1 contains the conservative DxL domain while BCMA2 is the segment outside the main functional area...
March 1, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28260100/expression-profile-of-baff-in-peripheral-blood-from-patients-of-iga-nephropathy-correlation-with-clinical-features-and-streptococcus%C3%A2-pyogenes-infection
#15
Nuoyan Zheng, Jinjin Fan, Bing Wang, Dongxian Wang, Pinning Feng, Qiongqiong Yang, Xueqing Yu
B cells are critically important for the pathogenesis of IgA nephropathy (IgAN). The present study aimed to investigate the abundance of B cell activating factor (BAFF), which belongs to the tumor necrosis factor superfamily, in the peripheral blood of patients with IgAN. The different forms of BAFF in peripheral blood and its association with clinical features and immunological factors were analyzed. mRNA levels of BAFF and other associated genes in the peripheral blood mononuclear cells (PBMCs) of patients with IgAN and controls were analyzed by quantitative polymerase chain reaction...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28249164/baff-and-taci-dependent-processing-of-baffr-by-adam-proteases-regulates-the-survival-of-b-cells
#16
Cristian R Smulski, Patrick Kury, Lea M Seidel, Hannah S Staiger, Anna K Edinger, Laure Willen, Maximilan Seidl, Henry Hess, Ulrich Salzer, Antonius G Rolink, Marta Rizzi, Pascal Schneider, Hermann Eibel
B cell activating factor (BAFF) provides B cells with essential survival signals. It binds to three receptors: BAFFR, TACI, and BCMA that are differentially expressed by B cell subsets. BAFFR is early expressed in circulating B cells and provides key signals for further maturation. Here, we report that highly regulated BAFFR processing events modulate BAFF responses. BAFFR processing is triggered by BAFF binding in B cells co-expressing TACI and it is executed by the metalloproteases ADAM10 and ADAM17. The degree of BAFF oligomerization, the expression of ADAM proteins in different B cell subsets, and the activation status of the cell determine the proteases involved in BAFFR processing...
February 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28245862/presence-of-an-interferon-signature-in-individuals-who-are-anti-nuclear-antibody-positive-lacking-a-systemic-autoimmune-rheumatic-disease-diagnosis
#17
Joan Wither, Sindhu R Johnson, Tony Liu, Babak Noamani, Dennisse Bonilla, Larissa Lisnevskaia, Earl Silverman, Arthur Bookman, Carolina Landolt-Marticorena
BACKGROUND: Elevated levels of type I interferons (IFNs) are a characteristic feature of the systemic autoimmune rheumatic diseases (SARDs) and are thought to play an important pathogenic role. However, it is unknown whether these elevations are seen in anti-nuclear antibody-positive (ANA(+)) individuals who lack sufficient criteria for a SARD diagnosis. We examined IFN-induced gene expression in asymptomatic ANA(+) individuals and patients with undifferentiated connective tissue disease (UCTD) to address this question...
February 28, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28245413/-research-progress-in-transgenic-animal-models-of-chronic-lymphocytic-leukemia-review
#18
Fang-Tian Wu, Wei Xu, Jian-Yong Li
Transgenic mouse models of chronic lymphocytic leukemia (CLL) are crucially required for the elucidation of the underlying pathogenic mechanisms and for finding new therapies. So far, several mouse models have been established, mimicking either genetic aberrations or dysregulated gene expression in CLL. Among all the models, TCL1 transgenic model is the most commonly used one. Additionally, there are also other models, such as 13q14-deletion model. In this review, the major genetically engineered mouse models of CLL in current use are summarized, the main problems include TCL-1 transgenic mice, miR15a/16-1 gene knockdown mice and miR29 transgeneic mice, BAFF and APRIL transgeneic mice, BCL-2:Traf2DN double transgeneic mice, IRF4(-/-)Vh11 transgeneic mice and so on...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28235864/baff-induces-tertiary-lymphoid-structures-and-positions-t-cells-within-the-glomeruli-during-lupus-nephritis
#19
SunAh Kang, Yuri Fedoriw, Ethan K Brenneman, Young K Truong, Kristine Kikly, Barbara J Vilen
Tissue-specific immune responses play an important role in the pathology of autoimmune diseases. In systemic lupus erythematosus, deposits of IgG-immune complexes and the activation of complement in the kidney have long been thought to promote inflammation and lupus nephritis. However, the events that localize cells in non-lymphoid tertiary organs and sustain tissue-specific immune responses remain undefined. In this manuscript, we show that BAFF promotes events leading to lupus nephritis. Using an inducible model of systemic lupus erythematosus, we found that passive transfer of antinucleosome IgG into AID(-/-)MRL/lpr mice elevated autoantibody levels and promoted lupus nephritis by inducing BAFF production in the kidneys, and the formation of renal tertiary lymphoid structures (TLSs)...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28215100/targeting-baff-and-april-in-systemic-lupus-erythematosus-and-other-antibody-associated-diseases
#20
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
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