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https://www.readbyqxmd.com/read/29774664/the-lupus-associated-fc%C3%AE-riib-i232t-polymorphism-results-in-impairment-in-the-negative-selection-of-low-affinity-germinal-center-b-cells-via-c-abl
#1
Jyun-Pei Jhou, I-Shing Yu, Haw Hwai, Chih-Shan Chen, Pei-Lung Chen, Shiang-Jong Tzeng
OBJECTIVE: FcγRIIB is an essential negative regulator of B cells to block BCR signaling and to trigger c-Abl-dependent apoptosis of B cells. FcγRIIB-deficient mice display splenomegaly with expansion of B cells, leading to lupus. FcγRIIB-I232T is a hypo-functional polymorphism associated with lupus susceptibility in humans, an autoimmune disease linked to diminished deletion of autoreactive B cells. In the context of FcγRIIB-I232T polymorphism, we investigated the role of FcγRIIB in the deletion of low-affinity germinal center (GC) B cells, an important mechanism for preventing autoimmunity...
May 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29762839/circulating-uca1-is-highly-expressed-in-patients-with-systemic-lupus-erythematosus-and-promotes-the-progression-through-the-akt-pathway
#2
C-R Jiang, T-H Li
OBJECTIVE: To investigate the role of Urothelial Carcinoma Associated 1 (UCA1) during the progression of systemic lupus erythematosus (SLE) and the underlying mechanism. PATIENTS AND METHODS: UCA1 expression in peripheral blood of SLE patients, as well as the expression of protein kinase B (AKT) in the peripheral blood mononuclear cell (PBMC), was detected by qRT-PCR. Expression differences in UCA1 and AKT between different groups were compared by t-test or univariate analysis...
April 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29724134/cigarette-smoking-and-the-pathogenesis-of-systemic-lupus-erythematosus
#3
Cameron B Speyer, Karen H Costenbader
Systemic lupus erythematosus (SLE) is a multi-system inflammatory autoimmune disease of incompletely understood etiology. It is thought that environmental exposures "trigger" or accelerate the disease in genetically-predisposed individuals. Areas covered: Substantial epidemiological evidence exists to support the association between cigarette smoking and the risk of incident SLE. Recent evidence points to current smoking as the specific risk factor, with decreasing risk 5 years after smoking cessation, and the greatest risk for disease characterized by the presence of SLE- specific autoantibodies...
May 3, 2018: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/29717110/il-21-drives-expansion-and-plasma-cell-differentiation-of-autoreactive-cd11c-hi-t-bet-b-cells-in-sle
#4
Shu Wang, Jingya Wang, Varsha Kumar, Jodi L Karnell, Brian Naiman, Phillip S Gross, Saifur Rahman, Kamelia Zerrouki, Richard Hanna, Christopher Morehouse, Nicholas Holoweckyj, Hao Liu, Zerai Manna, Raphaela Goldbach-Mansky, Sarfaraz Hasni, Richard Siegel, Miguel Sanjuan, Katie Streicher, Michael P Cancro, Roland Kolbeck, Rachel Ettinger
Although the aetiology of systemic lupus erythematosus (SLE) is unclear, dysregulated B cell responses have been implicated. Here we show that an unusual CD11chi T-bet+ B cell subset, with a unique expression profile including chemokine receptors consistent with migration to target tissues, is expanded in SLE patients, present in nephrotic kidney, enriched for autoreactive specificities and correlates with defined clinical manifestations. IL-21 can potently induce CD11chi T-bet+ B cells and promote the differentiation of these cells into Ig-secreting autoreactive plasma cells...
May 1, 2018: Nature Communications
https://www.readbyqxmd.com/read/29705243/a-kindred-with-mutant-ikaros-and-autoimmunity
#5
Erika Van Nieuwenhove, Josselyn E Garcia-Perez, Christine Helsen, Princess D Rodriguez, Pauline A van Schouwenburg, James Dooley, Susan Schlenner, Mirjam van der Burg, Els Verhoeyen, Rik Gijsbers, Seth Frietze, Hilde Schjerven, Isabelle Meyts, Frank Claessens, Stephanie Humblet-Baron, Carine Wouters, Adrian Liston
IKAROS (encoded by IKZF1) is an important hematopoietic transcription factor critical for early B cell differentiation, with major defects known to lead to low B cell numbers and hypogammaglobulinemia. More perplexing is the link between IKZF1 variants and autoimmunity, including polymorphisms associated with susceptibility to SLE, and recently, rare variants driving monogenic autoimmunity. We identified a novel p.L188V mutation in IKZF1 in the index patient and her father and found this mutation to lead to loss of DNA binding...
April 26, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29694256/associations-of-circulating-cxcr3-pd-1-cd4-t-cells-with-disease-activity-of-systemic-lupus-erythematosus
#6
Han Lei, Yang Xue, Yu Yiyun, Wan Weiguo, Lv Ling, Hejian Zou
OBJECTIVES: Which helper CD4+ T cell subset contributes to autoantibodies generation and severity of end-organ involvement in lupus patients remains to be explored. Our research aims to investigate the roles of circulating Tfh (cTfh) cell subsets and corresponding CXCR5- Th cells in lupus patients and their correlation with SLEDAI. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from blood of SLE patients as well as healthy donors. The proportion of Th cell Subsets classified from cell surface markers (CD45RO, CXCR5, CXCR3, CCR6, PD-1, ICOS, and CCR7) is detected by flow cytometry...
April 25, 2018: Modern Rheumatology
https://www.readbyqxmd.com/read/29660266/role-of-stem-cell-like-memory-t-cells-in-systemic-lupus-erythematosus
#7
Ye Ji Lee, Ji Ah Park, Hyunmi Kwon, Youn Soo Choi, Kyeong Cheon Jung, Seong Hoe Park, Eun Bong Lee
OBJECTIVE: Stem cell-like memory T (TSCM ) cells are long-lived memory T cells that have multipotent capacity to differentiate into different subsets. However, the role of TSCM cells in autoimmune diseases remains unclear. Here, we performed phenotypic studies to identify TSCM cells in patients suffering from systemic lupus erythematosus (SLE). METHODS: CD4+ and CD8+ TSCM cells were identified in SLE patients and healthy controls (HCs). In vitro culture systems, CD4+ TSCM cells were induced to differentiate into subsets of T cells, including follicular helper T (TFH ) cells and cytokine production pattern was measured after stimulation...
April 16, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29643853/gender-bias-in-human-systemic-lupus-erythematosus-a-problem-of-steroid-receptor-action
#8
Virginia Rider, Nabih I Abdou, Bruce F Kimler, Nanyan Lu, Susan Brown, Brooke L Fridley
Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease resulting from abnormal interactions between T and B cells. The acquisition of SLE is linked to genetic susceptibility, and diverse environmental agents can trigger disease onset in genetically susceptible individuals. However, the strongest risk factor for developing SLE is being female (9:1 female to male ratio). The female sex steroid, estradiol, working through its receptors, contributes to the gender bias in SLE although the mechanisms remain enigmatic...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29593737/overall-downregulation-of-mrnas-and-enrichment-of-h3k4me3-change-near-genome-wide-association-study-signals-in-systemic-lupus-erythematosus-cell-specific-effects
#9
Zhe Zhang, Lihua Shi, Li Song, Kelly Maurer, Michele A Petri, Kathleen E Sullivan
This study was designed to define gene expression and H3K4me3 histone modifications in T cells, B cells, and monocytes in systemic lupus erythematosus (SLE). Array studies of total peripheral blood mononuclear cells have demonstrated gene expression signatures related to neutrophils, interferon, and other inflammatory pathways. It is not clear how consistent these effects are across different cell types. In this study, RNA-seq and chromatin immunoprecipitation-seq were utilized to identify gene expression patterns and H3K4me3 histone modifications related to promoter activation in SLE...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29572548/t-cells-from-induced-and-spontaneous-models-of-sle-recognize-a-common-t-cell-epitope-on-%C3%AE-2-glycoprotein-i
#10
David Salem, Rebecca Subang, Masataka Kuwana, Jerrold S Levine, Joyce Rauch
Systemic lupus erythematosus is a prototypic model for B-cell epitope spread in autoimmunity. Autoantibodies to numerous molecularly distinct self-antigens emerge in a sequential manner over several years, leading to disease manifestations. Among the earliest autoantibodies to appear are those targeting phospholipid-binding proteins, particularly β2-glycoprotein I. Notably, mice immunized with β2-glycoprotein I and lipopolysaccharide develop a strong T cell response to β2-glycoprotein I that is associated with autoantibody production and renal disease, similar to that seen in human SLE...
March 23, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29563108/phase-iii-trial-results-with-blisibimod-a-selective-inhibitor-of-b-cell-activating-factor-in-subjects-with-systemic-lupus-erythematosus-sle-results-from-a-randomised-double-blind-placebo-controlled-trial
#11
Joan T Merrill, William R Shanahan, Morton Scheinberg, Kenneth C Kalunian, David Wofsy, Renee S Martin
BACKGROUND: Targeted inhibitors of B-cell activating factor (BAFF) have been evaluated in phase III trials in over 4000 patients with systemic lupus erythematosus (SLE). Post hoc analyses of these studies identify greater treatment effect in patients entering with higher disease activity, greater corticosteroid doses, anti double-stranded DNA (dsDNA) and low complement C3 or C4. OBJECTIVES: To evaluate the efficacy and safety of blisibimod, a BAFF inhibitor, in a population of patients with SLE enriched for high disease activity...
March 21, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29559975/tank-binding-kinase-1-dependent-responses-in-health-and-autoimmunity
#12
REVIEW
Cynthia Louis, Chris Burns, Ian Wicks
The pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is driven by genetic predisposition and environmental triggers that lead to dysregulated immune responses. These include the generation of pathogenic autoantibodies and aberrant production of inflammatory cytokines. Current therapies for RA and other autoimmune diseases reduce inflammation by targeting inflammatory mediators, most of which are innate response cytokines, resulting in generalized immunosuppression...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29558349/-epigenetic-disturbances-in-systemic-lupus-erythematosus
#13
Magdalena Dryglewska, Bogdan Kolarz, Maria Majdan
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that results in uncontrolled immune system activation and overproduction of autoantibodies. The pathogenesis of the disease is complex and not fully understood, nevertheless, genetic and environmental factors play an important role. So far, about 30 genes have been identified to be involved in the SLE pathomechanism. However, not all genetically predisposed individuals develop the disease. This phenomenon can be associated with epigenetic changes that occur under the influence of environmental factors...
2018: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29557491/a-meta-analysis-of-synovial-biomarkers-in-periprosthetic-joint-infection-synovasure%C3%A2-is-less-effective-than-the-elisa-based-alpha-defensin-test
#14
REVIEW
Sufian S Ahmad, Michael T Hirschmann, Roland Becker, Ahmed Shaker, Atesch Ateschrang, Marius J B Keel, Christoph E Albers, Lukas Buetikofer, Sithombo Maqungo, Ulrich Stöckle, Sandro Kohl
PURPOSE: (1) To determine the overall accuracy of synovial alpha-defensin, synovial C-reactive protein (sCRP), interleukin-6 (sIL-6), and leukocyte esterase (sLE) as diagnostic markers for periprosthetic joint infection (PJI) and (2) to independantly evaluate the accuracy of both the laboratory-based ELISA alpha-defensin test and the Synovasure™ alpha-defensin test kit. METHODS: An EMBASE and MEDLINE (PubMed) database search was performed using a set of professionally set search terms...
March 20, 2018: Knee Surgery, Sports Traumatology, Arthroscopy: Official Journal of the ESSKA
https://www.readbyqxmd.com/read/29556239/plasma-cell-differentiation-pathways-in-systemic-lupus-erythematosus
#15
REVIEW
Susan Malkiel, Ashley N Barlev, Yemil Atisha-Fregoso, Jolien Suurmond, Betty Diamond
Plasma cells (PCs) are responsible for the production of protective antibodies against infectious agents but they also produce pathogenic antibodies in autoimmune diseases, such as systemic lupus erythematosus (SLE). Traditionally, high affinity IgG autoantibodies are thought to arise through germinal center (GC) responses. However, class switching and somatic hypermutation can occur in extrafollicular (EF) locations, and this pathway has also been implicated in SLE. The pathway from which PCs originate may determine several characteristics, such as PC lifespan and sensitivity to therapeutics...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29526632/contribution-of-sex-steroids-and-prolactin-to-the-modulation-of-t-and-b-cells-during-autoimmunity
#16
REVIEW
Gabriela Recalde, Tamara Moreno-Sosa, Florencia Yúdica, Cristian A Quintero, María Belén Sánchez, Graciela A Jahn, Alexis M Kalergis, Juan Pablo Mackern-Oberti
In this review we discuss how sex steroids and prolactin affect regulation and responsiveness of B and T cells. Sex hormones exert profound effects on several physiological processes of non- reproductive tissues. In the immune system, several studies with experimental models for SLE have shown a noticeable pro-inflammatory role for ERα, contributing to disease development reflected in proteinuria and renal pathology. On the other hand, ERβ appears to have an anti- inflammatory and immunosuppressive effect...
May 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29513931/a-randomized-double-blind-parallel-group-placebo-controlled-multiple-dose-study-to-evaluate-amg-557-in-patients-with-systemic-lupus-erythematosus-and-active-lupus-arthritis
#17
Laurence E Cheng, Zahir Amoura, Benjamin Cheah, Falk Hiepe, Barbara A Sullivan, Lei Zhou, Gregory E Arnold, Wayne H Tsuji, Joan T Merrill, James B Chung
OBJECTIVE: Evaluate the safety and potential efficacy of AMG 557, a fully human antibody directed against the inducible T-cell costimulator ligand (ICOSL), in patients with systemic lupus erythematosus (SLE) with arthritis. METHODS: In this phase 1b, randomized, double-blind, placebo-controlled study, patients received AMG 557 210 mg (n=10) or placebo (n=10) weekly for 3 weeks, then every other week for 10 additional doses. Corticosteroids were tapered to ≤7...
March 7, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29503444/genetic-and-epigenetic-influences-on-the-loss-of-tolerance-in-autoimmunity
#18
REVIEW
Peng Zhang, Qianjin Lu
Immunological tolerance loss is fundamental to the development of autoimmunity; however, the underlying mechanisms remain elusive. Immune tolerance consists of central and peripheral tolerance. Central tolerance, which occurs in the thymus for T cells and bone marrow for B cells, is the primary way that the immune system discriminates self from non-self. Peripheral tolerance, which occurs in tissues and lymph nodes after lymphocyte maturation, controls self-reactive immune cells and prevents over-reactive immune responses to various environment factors...
March 5, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29482443/serum-soluble-cd25-as-a-risk-factor-of-renal-impairment-in-systemic-lupus-erythematosus-a-prospective-cohort-study
#19
R J Zhang, X Zhang, J Chen, M Shao, Y Yang, B Balaubramaniam, X L Sun, J L Ambrus, J He, Z G Li
Objective Serum soluble CD25 (sCD25) could be used as a biomarker for disease activity in conditions associated with T-cell activation including various autoimmune diseases. This study aimed to explore the role of sCD25 as an indicator of disease activity and organ involvement in patients with systemic lupus erythematosus (SLE). Methods Serum samples were collected from 107 SLE patients and 92 age-matched healthy controls (HCs). All patients were followed up for 24 weeks, and sCD25 was measured by enzyme-linked immunosorbent assay...
June 2018: Lupus
https://www.readbyqxmd.com/read/29481735/lgals9-deficiency-attenuates-nephritis-and-arthritis-in-pristane-induced-lupus-model-of-balb-c-mice
#20
Sonia Zeggar, Katsue S Watanabe, Sanae Teshigawara, Sumie Hiramatsu, Takayuki Katsuyama, Eri Katsuyama, Haruki Watanabe, Yoshinori Matsumoto, Tomoko Kawabata, Ken-Ei Sada, Toshiro Niki, Mitsuomi Hirashima, Jun Wada
OBJECTIVE: In systemic lupus erythematosus (SLE), an autoimmune disease associated with multiple organ involvements, lupus nephritis determines prognosis and arthritis impairs quality of life of patients. Galectin-9 (Gal-9, Lgals9) is a β-galactoside binding lectin and the attempts for its clinical application have been made in autoimmune diseases, since recombinant Gal-9 as a ligand for Tim-3 induces apoptosis in activated CD4+ Tim-3+ Th1 cell. We investigated wethere the deficiency of Lgals9 is beneficial or deleterious in lupus mice models...
February 26, 2018: Arthritis & Rheumatology
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