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https://www.readbyqxmd.com/read/29114388/epistatic-interactions-between-mutations-of-taci-tnfrsf13b-and-tcf3-result-in-a-severe-primary-immunodeficiency-disorder-and-systemic-lupus-erythematosus
#1
Rohan Ameratunga, Wikke Koopmans, See-Tarn Woon, Euphemia Leung, Klaus Lehnert, Charlotte A Slade, Jessica C Tempany, Anselm Enders, Richard Steele, Peter Browett, Philip D Hodgkin, Vanessa L Bryant
Common variable immunodeficiency disorders (CVID) are a group of primary immunodeficiencies where monogenetic causes account for only a fraction of cases. On this evidence, CVID is potentially polygenic and epistatic although there are, as yet, no examples to support this hypothesis. We have identified a non-consanguineous family, who carry the C104R (c.310T>C) mutation of the Transmembrane Activator Calcium-modulator and cyclophilin ligand Interactor (TACI, TNFRSF13B) gene. Variants in TNFRSF13B/TACI are identified in up to 10% of CVID patients, and are associated with, but not solely causative of CVID...
October 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29109527/the-rna-binding-protein-la-ss-b-promotes-rig-i-mediated-type-i-and-type-iii-ifn-responses-following-sendai-viral-infection
#2
Rebecca Mahony, Lindsay Broadbent, Jacen S Maier-Moore, Ultan F Power, Caroline A Jefferies
La/SS-B (or La) is a 48 kDa RNA-binding protein and an autoantigen in autoimmune disorders such as systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). La involvement in regulating the type I interferon (IFN) response is controversial - acting through both positive and negative regulatory mechanisms; inhibiting the IFN response and enhancing viral growth, or directly inhibiting viral replication. We therefore sought to clarify how La regulates IFN production in response to viral infection. ShRNA knockdown of La in HEK 293 T cells increased Sendai virus infection efficiency, decreased IFN-β, IFN-λ1, and interferon-stimulated chemokine gene expression...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29074827/-update-on-recent-progress-in-vitamin-d-research-the-effects-of-vitamin-d-in-autoinflammatory-diseases
#3
Tomoka Ao, Junichi Kikuta, Masaru Ishii
Various kinds of immune cells -including dendritic cells, macrophages, T cells and B cells- express the vitamin D receptor and 1α-hydroxylase(CYP27B1). In vitro studies have shown the anti-inflammatory effect of 1,25-dihydroxyvitamin D:the active form of vitamin D. As vitamin D deficiency spread in our society, epidemiological studies have established the association between vitamin D deficiency and incidence or progression of several inflammatory diseases, including rheumatoid arthritis(RA), systemic lupus erythematosus(SLE), and multiple sclerosis(MS)...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/29073347/efficacy-and-safety-of-atacicept-in-patients-with-systemic-lupus-erythematosus-results-of-a-24-week-randomized-placebo-controlled-phase-iib-study
#4
Joan T Merrill, Daniel J Wallace, Stephen Wax, Amy Kao, Patricia A Fraser, Peter Chang, David Isenberg
OBJECTIVE: To evaluate the efficacy and safety of atacicept, an antagonist of BLyS/APRIL-mediated B cell activation, in patients with systemic lupus erythematosus (SLE). METHODS: ADDRESS II was a phase IIb, multicentre study (NCT01972568). Patients with active, autoantibody-positive SLE receiving standard therapy were randomized (1:1:1) to atacicept (75 or 150 mg) or placebo for 24 weeks. The primary endpoint was the SLE responder index (SRI)-4 at Week 24. RESULTS: The ITT population included 306 patients...
October 26, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29069649/the-systemic-activation-of-programmed-death-1-pd-l1-axis-protects-systemic-lupus-erythematosus-model-from-nephritis
#5
Wenjun Liao, Hua Zheng, Sha Wu, Yanmei Zhang, Wei Wang, Zili Zhang, Chenfei Zhou, Hongjun Wu, Jie Min
BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by abnormal activated T cells, autoreactive B cells, and massive cytokines. The CD4+ T cells determined B-cells differentiation and cytokines production. The programmed death 1 (PD-1) is the checkpoint immunoinhibitory receptor of activated T cells, and its engagement could exhaust T cells. In this study, we investigated the role of PD-1 systemic engagement with PD-L1-Ig in lupus-like nephritis in SLE mice. METHODS: The murine PD-L1-Ig was injected into SLE-prone mice...
October 26, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/29066741/peripheral-cd19-hi-b-cells-exhibit-activated-phenotype-and-functionality-in-promoting-igg-and-igm-production-in-human-autoimmune-diseases
#6
Zhicui Liu, Weihong Zeng, Xiangyang Huang, Shujun Wang, Jie Zheng, Meng Pan, Ying Wang
Systemic Lupus Erythematosus (SLE) and pemphigus are two representative autoimmune diseases driven by pathogenic autoantibody systemically and organ-specifically, respectively. Given the involvement of antibody in the pathogenesis, B cells are inclined to differentiate and function in an abnormal activation model. Here we defined a unique CD19(hi) B cell population existing in the periphery of SLE and pemphigus patients as well as in human tonsils. CD19(hi) B cells could be induced in vitro after co-culturing fully activated CD4(+) T cells with autologous B cells...
October 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29045964/-increased-serum-c-c-chemokine-ligand-19-levels-correlated-with-b-cell-abnormalities-in-systemic-lupus-erythematosus
#7
H J Liu, L J Shi, F L Hu, H H Yao, Z G Li, Y Jia
OBJECTIVE: To detect the levels of serum C-C chemokine ligand 19 (CCL19) in patients with systemic lupus erythematosus (SLE) and to evaluate the correlation between CCL19 expression and clinical features and laboratory parameters, trying to reveal the possible role of CCL19 in the pathogenesis of systemic lupus erythematosus. METHODS: The levels of serum CCL19 were measured by enzyme linked immunosorbent assay (ELISA) in 90 patients with SLE and 30 healthy controls...
October 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/29045736/clinical-trial-parameters-that-influence-outcomes-in-lupus-trials-that-use-the-systemic-lupus-erythematosus-responder-index
#8
Kenneth C Kalunian, Murray B Urowitz, David Isenberg, Joan T Merrill, Michelle Petri, Richard A Furie, Mary-Ann Morgan-Cox, Rebecca Taha, Steven Watts, Maria Silk, Matthew D Linnik
Objective: The SLE Responder Index (SRI) is a composite endpoint used in SLE trials. This investigation examined the clinical trial elements that drive response measured by the SRI. Methods: Analyses are based on data from two phase 3 trials (n = 2262) that evaluated the impact of an anti-B-cell activating factor antibody on disease activity using SRI-5 as the primary endpoint (ClinicalTrials.gov NCT01196091 and NCT01205438). Results: The SRI-5 response rate at week 52 for all patients was 32...
October 17, 2017: Rheumatology
https://www.readbyqxmd.com/read/29020082/expression-patterns-of-signaling-lymphocytic-activation-molecule-family-members-in-peripheral-blood-mononuclear-cell-subsets-in-patients-with-systemic-lupus-erythematosus
#9
Maria P Karampetsou, Denis Comte, Katalin Kis-Toth, Vasileios C Kyttaris, George C Tsokos
Genome-wide linkage analysis studies (GWAS) studies in systemic lupus erythematosus (SLE) identified the 1q23 region on human chromosome 1, containing the Signaling Lymphocytic Activation Molecule Family (SLAMF) cluster of genes, as a lupus susceptibility locus. The SLAMF molecules (SLAMF1-7) are immunoregulatory receptors expressed predominantly on hematopoietic cells. Activation of cells of the adaptive immune system is aberrant in SLE and dysregulated expression of certain SLAMF molecules has been reported...
2017: PloS One
https://www.readbyqxmd.com/read/29018507/down-regulation-of-mbd4-contributes-to-hypomethylation-and-overexpression-of-cd70-in-cd4-t-cells-in-systemic-lupus-erythematosus
#10
Wei Liao, Mengying Li, Haijing Wu, Sujie Jia, Nu Zhang, Yong Dai, Ming Zhao, Qianjin Lu
BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by lymphocytic infiltration and overproduction of autoantibodies, leading to significant morbidity and mortality. However, the pathogenesis of this disorder has not yet been completely elucidated. It has been reported that CD70, a B cell costimulatory molecule encoded by the gene TNFSF7 (tumor necrosis factor ligand superfamily member 7), is overexpressed in CD4(+) T cells from patients with SLE due to the demethylation of its promoter...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28987592/cathepsin-s-inhibition-suppresses-autoimmune-triggered-inflammatory-responses-in-macrophages
#11
Sophia Thanei, Michel Theron, Ana Patricia Silva, Bernhard Reis, Leonore Branco, Lucia Schirmbeck, Fabrice A Kolb, Wolfgang Haap, Thomas Schindler, Marten Trendelenburg
In several types of antigen-presenting cells (APCs), Cathepsin S (CatS) plays a crucial role in the regulation of MHC class II surface expression and consequently influences antigen (Ag) presentation of APCs to CD4(+) T cells. During the assembly of MHC class II-Ag peptide complexes, CatS cleaves the invariant chain p10 (Lip10) - a fragment of the MHC class II-associated invariant chain peptide. In this report, we used a selective, high-affinity CatS inhibitor to suppress the proteolytic activity of CatS in lymphoid and myeloid cells...
October 4, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28984923/b-cell-tolerance-to-epidermal-ribonuclear-associated-neo-autoantigen-in-vivo
#12
Søren E Degn, Elisabeth Alicot, Michael C Carroll
Defining how self-antigens are perceived by the immune system is pivotal to understand how tolerance is maintained under homeostatic conditions. Clinically relevant, natural autoantigens targeted by autoantibodies in e.g. systemic lupus erythematosus (SLE) commonly have an intrinsic ability to engage not only the B cell receptor (BCR), but also a costimulatory pathway in B cells, such as the TLR7 pathway. Here we developed a novel mouse model displaying inducible expression of a fluorescent epidermal neo-autoantigen carrying an OT-II T cell epitope, B cell antigen, and associated ribonucleic acids capable of stimulating TLR7...
October 6, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28944101/soluble-micb-in-plasma-and-urine-explains-population-expansions-of-nkg2d-cd4-t-cells-inpatients-with-juvenile-onset-systemic-lupus-erythematosus
#13
Satoru Hamada, Andrea Caballero-Benitez, Kate L Duran, Anne M Stevens, Thomas Spies, Veronika Groh
Abnormal NKG2D ligand expression has been implicated in the initiation and maintenance of various auto-inflammatory disorders including systemic lupus erythematosus (SLE). This study's goal was to identify the cellular contexts providing NKG2D ligands for stimulation of the immunosuppressive NKG2D(+)CD4 T cell subset that has been implicated in modulating juvenile-onset SLE disease activity. Although previous observations with NKG2D(+)CD4 T cells in healthy individuals pointed towards peripheral B cell and myeloid cell compartments as possible sites of enhanced NKG2DL presence, we found no evidence for a disease-associated increase of NKG2DL-positivity among juvenile-onset SLE B cells and monocytes...
March 2017: Open Journal of Immunology
https://www.readbyqxmd.com/read/28940360/lys63-polyubiquitination-by-the-e3-ligase-casitas-b-lineage-lymphoma-b-cbl-b-modulates-peripheral-regulatory-t-cell-tolerance-in-patients-with-systemic-lupus-erythematosus
#14
Jorge Romo-Tena, Sandra Rajme-López, Luis Aparicio-Vera, Jorge Alcocer-Varela, Diana Gómez-Martín
T cells from systemic lupus erythematosus (SLE) patients display a wide array of anomalies in peripheral immune tolerance mechanisms. It has recently been described the role of ubiquitin ligases such as Cbl-b in these phenomena. However, its role in resistance to suppression phenotype in SLE has not been characterized, which was the aim of the present study. Thirty SLE patients (20 with active disease and 10 with complete remission) and 30 age- and sex-matched healthy controls were recruited. Effector (CD4+CD25-) and regulatory (CD4+CD25+) T cells were purified from PBMCs by magnetic selection...
September 23, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28910360/transgelin-2-is-upregulated-on-activated-b-cells-and-expressed-in-hyperplastic-follicles-in-lupus-erythematosus-patients
#15
Kaori Kiso, Hajime Yoshifuji, Takuma Oku, Masaki Hikida, Koji Kitagori, Yoshitaka Hirayama, Toshiki Nakajima, Hironori Haga, Tatsuaki Tsuruyama, Aya Miyagawa-Hayashino
Transgelin-2 (TAGLN2) is an actin-binding protein that controls actin stability and promotes T cell activation. TAGLN2 is also expressed on B-cells but its function in B-cells is unknown. We found that TAGLN2-expressing B-cells were localized in the germinal center (GC) of secondary lymphoid tissues and TAGLN2 mRNA was significantly upregulated after IgM+IgG stimulation in primary human B-cells, suggesting that TAGLN2 was upregulated upon B-cell activation. In support of this, lymph nodes (LNs) from patients with systemic lupus erythematosus (SLE), in which the intense GC activity have been recognized, showed increased TAGLN2 expression in B-cells compared to control LNs...
2017: PloS One
https://www.readbyqxmd.com/read/28899868/b-cell-derived-il-6-initiates-spontaneous-germinal-center-formation-during-systemic-autoimmunity
#16
Tanvi Arkatkar, Samuel W Du, Holly M Jacobs, Elizabeth M Dam, Baidong Hou, Jane H Buckner, David J Rawlings, Shaun W Jackson
Recent studies have identified critical roles for B cells in triggering autoimmune germinal centers (GCs) in systemic lupus erythematosus (SLE) and other disorders. The mechanisms whereby B cells facilitate loss of T cell tolerance, however, remain incompletely defined. Activated B cells produce interleukin 6 (IL-6), a proinflammatory cytokine that promotes T follicular helper (TFH) cell differentiation. Although B cell IL-6 production correlates with disease severity in humoral autoimmunity, whether B cell-derived IL-6 is required to trigger autoimmune GCs has not, to our knowledge, been addressed...
November 6, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28885337/b-cell-lymphocyte-kinase-polymorphisms-rs13277113-rs2736340-and-rs4840568-and-risk-of-autoimmune-diseases-a-meta-analysis
#17
Chang Zeng, Cheng Fang, Hong Weng, Xiaoqing Xu, Tianyang Wu, Wenhua Li
BACKGROUND: B-cell lymphocyte kinase (BLK) is an inhibitor of B cells that has an important influence on several autoimmune diseases, but there is a lack of comprehensive analysis of its association with autoimmune diseases. Hence, it is meaningful to conduct a comprehensive analysis. METHODS: A systematic literature search was performed on the PubMed, ScienceDirect, and Web of Science databases up to June 30, 2016. The data were extracted and quality-assessed before conducting the meta-analysis...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28876451/selective-hdac6-inhibition-decreases-early-stage-of-lupus-nephritis-by-downregulating-both-innate-and-adaptive-immune-responses
#18
Jingjing Ren, Xiaofeng Liao, Miranda D Vieson, Miao Chen, Reilly Scott, Jillian Kazmierczak, Xin M Luo, Christopher M Reilly
We have previously demonstrated that HDAC6 expression is increased in animal models of systemic lupus erythematosus (SLE) and that inhibition of HDAC6 decreased disease. In our current studies, we tested if an orally active selective HDAC6 inhibitor would decrease disease pathogenesis in a lupus mouse model with established early disease. Additionally, we sought to delineate the cellular and molecular mechanism(s) of action of a selective HDAC6 inhibitor in SLE. We treated 20-week-old (early-disease) NZB/W F1 female mice with two different doses of the selective HDAC6 inhibitor (ACY-738) for five weeks...
September 6, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28859258/lupus-associated-functional-polymorphism-in-pnp-causes-cell-cycle-abnormalities-and-interferon-pathway-activation-in-human-immune-cells
#19
Yogita Ghodke-Puranik, Jessica M Dorschner, Danielle M Vsetecka, Shreyasee Amin, Ashima Makol, Floranne Ernste, Thomas Osborn, Kevin Moder, Vaidehi Chowdhary, Elias Eliopoulos, Maria I Zervou, George N Goulielmos, Mark A Jensen, Timothy B Niewold
OBJECTIVE: Systemic lupus erythematosus (SLE) is frequently characterized by activation of the type I interferon (IFN) pathway. We previously observed that a missense single-nucleotide polymorphism (rs1049564) in the purine nucleoside phosphorylase (PNP) gene was associated with high levels of IFN in SLE. PNP is a key enzyme involved in purine metabolism. In this study, we performed functional follow-up of this polymorphism in human cells. METHODS: Type I IFN was measured in patient sera, using a reporter cell assay...
August 31, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28853005/unmet-needs-in-the-pathogenesis-and-treatment-of-systemic-lupus-erythematosus
#20
REVIEW
Jyoti Bakshi, Beatriz Tejera Segura, Christopher Wincup, Anisur Rahman
Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease with a prevalence of approximately 1 in 1000. Over the last 30 years, advances in treatment such as use of corticosteroids and immunosuppressants have improved life expectancy and quality of life for patients with lupus and the key unmet needs have therefore changed. With the reduced mortality from disease activity, development of cardiovascular disease (CVD) has become an increasingly important cause of death in patients with SLE. The increased CVD risk in these patients is partly, but not fully explained by standard risk factors, and abnormalities in the immune response to lipids may play a role...
August 29, 2017: Clinical Reviews in Allergy & Immunology
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