Rationale For B Cell Targeting In SLE
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bodies, anti-B-Cell therapies have emerged as a new option for treating autoimmune diseases. The rationale for this changeover from T-Cell to B-Cell targeted therapies resides in the recently accumulated evidence of the role of B-Cells in the pathogenesis of autoimmune diseases and in the generation of tissue damage. Targeting memory and
REVIEW Rationale of anti-CD19 immunotherapy: an option to
levels [12-15]. Th e clinical value of belimumab in SLE  could also involve targeting of B-cell functions other than autoantibody production. In this regard, B-cell development at the stage of transitional B cells is aﬀ ected by this treatment . Based on the serum Ig data serving as a surrogate
Advances in Systemic Lupus Erythematosus (SLE): A case for
rationale of targeting IFN-a in SLE, with significant re-ductions in lupus activity, but also an increased risk for herpes zoster infections. Our prediction is that targeting IFN-α may prove useful as an add-on therapy to stan-dard regimens in SLE, to accomplish deeper remission and prevent flares. LUPUS THROMBOCYTOPENIA
Rituximab in the treatment of anti-neutrophil cytoplasm
SLE can also be found. In AASV, abnormal B-cell clusters adjacent to proteinase 3 (PR3)-ANCA-positive cells and plasma cells have been observed in nasal biopsies.3 Addi-tionally, the regulation of T lymphocytes, known to be important in AASV, is interdependent on B-cell function.4,5 In SLE, abnormalities of B-cell interactions with antigen-
REVIEW B-cell depletion in SLE: clinical and trial experience
pathogenic B-cell subsets are therefore not likely to be available in the near future. Th is reality provides the rationale for targeting B cells in patients with SLE, RA and other autoimmune diseases [1-5]. B-cell-targeted immunotherapy was initially developed for the treatment of B-cell-related malignancies, which
Neutralization of B-Cell Activating Factor (BAFF) by
Sep 23, 2020 necrosis factor (TNF) family member B-cell activating factor (BAFF) to play a major role for survival of both healthy and malignant B cells [13 16]. BAFF binds to three di erent receptors: the BAFF receptor (BAFFR), transmembrane activator and cyclophilin ligand interactor (TACI), and B-cell maturation antigen (BCMA).
Ectopic lymphoid-like structures in infection, cancer and
Jun 20, 2014 SLE Tubulointerstitium of the kidneys Human Mouse Immunoglobulin repertoire analysis reveals B cell clonal expansion and ongoing somatic hypermutation 130,165 Chronic inflammation Atherosclerosis Aorta Human Mouse Unknown Cellular organization LTβR, CXCL13 and CCL21 expression 166,167 Inflammatory bowel disease Gut
A perspective on B-cell-targeting therapy for SLE
A perspective on B-cell-targeting therapy for SLE R. John Looney Æ Jennifer Anolik Æ Inaki Sanz Received: 7 July 2009/Accepted: 13 July 2009/Published online: 8 August 2009 Japan College of Rheumatology 2009 Abstract In recent years, large controlled trials have tested several new agents for systemic lupus erythematosus (SLE).
Cronicon CANCER OPEN ACCESS Opinion STAT3 Inhibitors for
STAT3 Inhibitors for Cancer Therapy the Rationale and Remained Problems S2 Citation: Tomohiro Chiba. STAT3 Inhibitors for Cancer Therapy the Rationale and Remained Problems EC Cancer 1.S1 (2016): S1-S8. Another noteworthy aspect of STAT3 is the critical involvement in the tumor microenvironment. As cytokines are regulators of in-
Mechanisms of action of intravenous immunoglobulin therapy
activated cell sorting showed that the suppressor activity resided in the CD8-positive T-cell fraction. All patients had an intrinsic B-cell defect, and the effects of IVIG ther- apy on B-cell function could not be studied. TABLE 2. Mechanisms of Action of Intravenous Immunoglobulin Fc receptor blockade of reticuloendothelial cell system and
th Annual Meeting of the Lupus Academy Meeting Report
of refractory SLE which would be discussed further during the course of the meeting.3 4. A miss with BLys BLyS is crucial to B-cell maturation, differentiation and survival, providing a solid biological rationale for targeting BLyS in SLE.4-7 Murine models have shown that transgenic mice develop SLE-like disease
Creation of a Retroviral RNAi Knockdown System to Investigate
1.1 Systemic Lupus Erythematosus Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disorder characterized by the production of autoantibodies to cellular components, including double-stranded and single-stranded DNA [1, 2]. These autoantibodies form immune complexes with nucleic acids and
An update on the management of systemic lupus erythematosus
Numerous mechanisms lead to B-cell hyperactivity, including loss of immune self-tolerance and high antigenic load consisting of environmental and self-antigens presented to B cells by other B cells or specific antigen-presenting cells. There is a move of the T cell function towards B cell function leading to intensified autoantibody production.
Anti-B-Cell Therapies in Autoimmune Neurological Diseases
has been the availability of new biological agents targeting B cells or B-cell pathways, highlighting the role of B-cell auto-immunity in the pathophysiology of neurological disorders and offering exciting new therapeutic interventions. This paper provides an overview of B-cell biology; ad-dresses the role of B cells in autoimmune neurological
Belimumab for the treatment of systemic lupus erythematosus
of systemic lupus erythematosus (SLE) as well as multiple other autoimmune diseases. Owing to the multitude of evidence showing B‑cell dysfunction in SLE, targeting B cells has been investigated as a modality for treating the disease. There are a number of strategies that can be used for B‑cell‑directed therapy.
B-cell-targeted therapies: promising new treatments for
CD27 is a B-cell costimulatory molecule of the TNF receptor family that binds CD70 as its ligand and effects the activation of T cells [14,15]. Targeting B cells in active SLE is thus a rational therapeutic strategy. B-cell targeting methods CD20 CD20 appears on the surface of the pre-B lym-phocyte, between the time of light-chain rear-
Targeting the Splicing of mRNA in Autoimmune Diseases - Cell
B lymphocyte stimulator (BLyS)), an interferon-inducible cyto-kine, is essential for autoreactive B-cell activation, survival, and autoantibody secretion. Interestingly, BAFF also plays a patho-genic role in lymphomas. BAFF transgenic mice spontaneously develop SLE- and SS-like symptoms. 2,3 In patients with pSS, BAFF
IL-7 in Rheumatoid Arthritis: Pathogenesis, Biomarker and
ATK- Protein Kinase B Bcl2- B-cell lymphoma 2 BM-Bone marrow CD3, 4, 28, 127- cluster of differentiation 3, 4, 28 and 127 CDC25- Cell division cycle 25 phosphatase CIA- collagen induced arthritis DAS44- Disease activity score 44 MTX- methotrexate DCs-dendritic cells DM1- Diabetes mellitus type 1 DMARD- Disease-modifying anti-rheumatic drugs
The Role of Immune Checkpoint Receptors in Regulating Immune
Figure 1. Co-signaling axes of T cells driving systemic lupus erythematosus (SLE). T cell is initially activated by the bridging between the T cell receptor (TCR) and major histocompatibility complex (MHC) on the surface of antigen-pres enting cells (APCs). Besides this first signal, T cell activity could
Developing novel drugs for systemic lupus erythematosus
in B-cell subsets have been described in SLE, and active disease is accompanied by depletion of naïve B-cells and expansion of peripheral memory and plasma B-cells . Figure 1. Differential receptor expression during subsequent phases of B-cell development. Before
2017-18 - Alliance for Lupus Research
Autophagy Components and B cell Activation during SLE Natalia Giltiay, PhD University of Washington, Seattle, WA Anti-BDCA 2-Targeted Therapy for SLE Shaun Jackson, MD, PhD Seattle Children s Hospital, Seattle, WA B Cell-Intrinsic Cytokine Reg of Spontaneous Germinal Ctr Formation in SLE Andrea Knight, MD The Children s Hospital of
Long‐Term Safety and Efficacy of Epratuzumab in the Treatment
necrosis factor cytokine production (15,16). B cell hyperac-tivity and altered cytokine production play a pivotal role in active SLE (17), ergo there is a strong rationale for targeting CD22-mediatedBcellsignalinginSLE. The safety and efﬁcacy of epratuzumab have been assessed in the ALLEVIATE-1 and -2 randomized controlled trials
Safety and Efficacy of SBI-087, a Subcutaneous Agent for B
peripheral B cell counts. B cells were obtained at baseline and weeks 2, 4, 8, 12, 16, and 24, and were quantified using a high-sensitivity flow cytometry assay with a lower limit of quantification of 0.3 cells/μl. Safety evaluations included adverse events (AE), serious AE (SAE), safety laboratory tests, physical examinations, and vital signs.
Rationale for CD40 pathway blockade in autoimmune rheumatic
reported in many autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and Sjögren s syndrome, thus supporting its role in the breach of immune tolerance that is typical of these diseases. Targeting CD40 CD40L signalling might represent a novel therapeutic option for several autoimmune disorders. Introduction
Targeting Neutrophil Adhesive Events to Address Vaso
Targeting Neutrophil Adhesive Events to Address Vaso-Occlusive Crisis in Sickle Cell Patients Vasilios A. Morikis 1, Alfredo A. Hernandez , John L. Magnani2, Markus Sperandio3 and Scott I. Simon1* 1 Department of Biomedical Engineering, University of California-Davis, Davis, CA, United States, 2 GlycoMimetics Inc.,
Systematic review of safety and efficacy of belimumab in
dependent B-cell responses to certain antigens, regulation of the B-cell compartment, and immunoglobulin (Ig) class switching (also called class-switch recombination). Thus, therapeutic use of beli - mumab interferes with the homeostasis of immature and mature B cells and plasma cells, while sparing B-cell progenitors and mem - ory B cells.
B Cell Aberrance in Lupus: the Ringleader and the Solution
as well as intracellular signal pathways involved in B cell biology, are all contributing to B cell aberrance and participating in the pathogenesis of SLE. Based on that rationale, targeting aberrance of B cells and relevant molecules and pathways is expected to be a promising strategy for lupus control.
A cytotoxic anti-IL-3Rα antibody targets key cells and
To date, the major target of biologic therapeutics in systemic lupus erythematosus (SLE) has been the B cell, which produces pathogenic autoantibodies. Recently, targeting type I IFN, which is elaborated by plasmacytoid dendritic cells (pDCs) in response to endosomal TLR7 and TLR9 stimulation by SLE immune complexes, has shown promising results
Review Double anti-B cell and anti-BAFF targeting for the
B cells, promotes survival and develop - ment of transitional and mature B cells. BR3 (but not TACI and BCMA) is also expressed on the surface of effector memory T cells, costimulating T-cell proliferation and cytokines secretion as well (40, 44-46). TACI is expressed mainly on memory B cells and on naïve B cells at steady state (47). TACI sig-
Moving Forward With Biologics in Lupus Nephritis
monoclonals directed against B-cell surface marker CD20. The biologics targeting B-cell activation and maturation block interactions between B-cell ligands and their corresponding B-cell receptors. Ligands targeted include BLyS (B-lymphocyte stimulator), also known as BAFF (B-cell activating factor), and APRIL (A proliferation-inducingligand).
University of Birmingham Rationale for CD40 pathway blockade
1. CD40/CD40L signalling pathway regulates immune and non-immune cell responses 2. CD40/CD40L signalling is altered in autoimmune diseases such as SLE, RA, and SS 3. Early clinical trials programmes targeting CD40L were halted due to thrombotic adverse events 4. New therapeutic approaches targeting CD40 or using modified molecules against CD40L are
Abstracts - Lupus Science & Medicine
immunity. Here disturbances in cytokine production and B lineage cell disturbances became very evident in recent years. Identification of increased interleukin (IL)-6, IL-17, IL-12 and IL-23, BAFF, and especially type I interferon (IFN) production by different cell types, provided the rationale for targeting these cytokines or their correspond-
The Texas Medical Center Library [email protected] The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Ope
Zahi Touma, Dafna D Gladman - BMJ
ment of SLE, lupus nephritis and cutaneous lupus (tables 1 and 2). In phase III trials, agents include those targeting the interferon (IFN) pathway, BAFF-APRIL pathway, T-cell signalling and B-cell signalling. Furthermore, combinations of novel agents that target different mech-anisms of action are being explored in phase II trials, as
Interferon- ExcessLeadstoPathogenicAccumulation - Cell
aberrant Tfh cell formation provides a rationale for IFN-g blockade in lupus patients with an overactive Tfh cell-associated pathway. INTRODUCTION Systemic lupus erythematosus (SLE) is a heterogeneous auto-immune disease caused by autoantibodies targeting nuclear components that affect multiple organs (Rahman and Isenberg, 2008).
lup.sagepub.com LETTER TO THE EDITOR
(PCs) and memory B cells) are found due to the early interruption of the B-cell receptor (BCR) intracellular signalling pathway.8 On the other hand, the targeting of CD20 on rituximab therapy may drive an extensive suppression of B cells either at immature, transitional, naı¨ve or memory stage, while sparing pro-B, pre-B, bone marrow long-lived
The Role of BAFF in B cell Biology and Autoimmunity
B-cell targeted therapeutics in clinical development. Arthritis Res Ther 15 Suppl 1: S4. Davidson, A. (2012). The rationale for BAFF inhibition in systemic lupus erythematosus. Curr Rheumatol Rep 14(4): 295-302. Krivosikova, M., T. Dallos, W. Maslinski and M. Buc (2009). B cell activating factor, its role in
CELL BIOLOGY Copyright © 2020 Inhibition of IRF5 cellular
role in TLR9/B cell receptor induced plasmablast differentiation and antibody secretion (12, 47). Collectively, these findings pro-vide a compelling rationale for the development of therapeutic agents targeting IRF5 for the treatment of SLE and other auto-immune diseases. Thus far, preclinical studies have relied entirely on the use of small