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https://www.readbyqxmd.com/read/28300427/annexin-a1-as-a-target-for-managing-murine-pristane-induced-systemic-lupus-erythematosus
#1
Nikolina Mihaylova, Silviya Bradyanova, Petroslav Chipinski, Melinda Herbáth, Stela Chausheva, Dobroslav Kyurkchiev, József Prechl, Andrey I Tchorbanov
Systemic lupus erythematosus (SLE) is a polygenic pathological disorder which involves multiple organs. Self-specific B cells play a main role in the lupus pathogenesis by generating autoantibodies as well as by serving as important autoantigen-presenting cells. Autoreactive T lymphocytes, on the other hand, are responsible for B cell activation and proliferation, and cytokine production. Therefore, both factors promote the idea that a down-modulation of activated self-reactive T and B cells involved in the pathogenic immune response is a reasonable approach for SLE therapy...
March 16, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28296250/different-genetic-alteration-of-a20-in-a-s%C3%A3-zary-syndrome-case-with-v%C3%AE-2-j%C3%AE-22-t-cell-clone
#2
Lingling Zhou, Haitao Zheng, Xin Huang, Lihua Zhu, Suijing Wu, Chengwu Zeng, Lijian Yang, Shaohua Chen, Gengxin Luo, Xin Du, Yangqiu Li
BACKGROUND: The comprehensive genetic alterations underlying the pathogenesis of Sézary syndrome (SS) remains largely unknown. Previous studies showed that alterations of tumor necrosis factor-α-induced protein 3 gene (TNFAIP3; A20) are frequent in SS. In this study, we characterized the mutation and polymorphisms of A20 in a case with SS and compared with the genetic feature of A20 in T-cell acute lymphoblastic leukemia (T-ALL). METHODS: Using a novel approach based on the combination of fine-tiling array comparative genomic hybridization ( and ligation-mediated polymerase chain reaction (LM-PCR) to identify SS clone, the polymorphisms in the A20 gene (promoter, exons 2-9 [coding region] and 3'UTR) were detected by PCR and sequencing...
March 14, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28293460/pauci-immune-lupus-nephritis-possibility-or-co-incidence
#3
Döndü Üsküdar Cansu, Gökhan Temiz, Mustafa F Açıkalın, Cengiz Korkmaz
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized with immune complex formation and renal involvement of lupus and may include several kinds of pathological conditions, but mostly, it is associated with immune complex-induced glomerular disease. Pauci-immune lupus nephritis is a very rare condition. We describe a 45-year-old female patient with pauci-immune crescentic necrotizing lupus nephritis and briefly discuss the possible mechanism and pathogenesis.
March 2017: European Journal of Rheumatology
https://www.readbyqxmd.com/read/28286780/il-1%C3%AE-and-il-6-are-highly-expressed-in-rf-ige-systemic-lupus-erythematous-subtype
#4
Yongkang Wu, Bei Cai, Junlong Zhang, Beilei Shen, Zhuochun Huang, Chunyu Tan, Carla C Baan, Lanlan Wang
Background. Systemic lupus erythematosus (SLE) is an autoimmune disease with great heterogeneity in pathogenesis and clinical symptoms. Rheumatoid factor (RF) is one key indicator for rheumatoid arthritis (RA) while immunoglobulin E (IgE) is associated with type I hypersensitivity. To better categorize SLE subtypes, we determined the dominant cytokines based on familial SLE patients. Methods. RF, IgE, and multiple cytokines (i.e., IL-1β, IL-6, IL-8, IL-10, IL-17, IFN-γ, IP-10, MCP-1, and MIP-1β) were measured in sera of familial SLE patients (n = 3), noninherited SLE patients (n = 108), and healthy controls (n = 80)...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28283529/targeting-the-rhoa-rock-pathway-to-reverse-t-cell-dysfunction-in-sle
#5
Cristina Rozo, Yurii Chinenov, Reena Khianey Maharaj, Sanjay Gupta, Laura Leuenberger, Kyriakos A Kirou, Vivian P Bykerk, Susan M Goodman, Jane E Salmon, Alessandra B Pernis
OBJECTIVES: Deregulated production of interleukin (IL)-17 and IL-21 contributes to the pathogenesis of autoimmune disorders such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Production of IL-17 and IL-21 can be regulated by ROCK2, one of the two Rho kinases. Increased ROCK activation was previously observed in an SLE cohort. Here, we evaluated ROCK activity in a new SLE cohort, and an RA cohort, and assessed the ability of distinct inhibitors of the ROCK pathway to suppress production of IL-17 and IL-21 by SLE T cells or human Th17 cells...
April 2016: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28279839/comorbid-association-of-antiphospholipid-antibodies-and-migraine-a-systematic-review-and-meta-analysis
#6
REVIEW
Md Asiful Islam, Fahmida Alam, Kah Keng Wong
BACKGROUND: Antiphospholipid antibodies (aPLs) namely anticardiolipin (aCL) antibody, anti-β2-glycoprotein I (β2GPI) antibody and lupus anticoagulant (LA) are autoantibodies produced against anionic phospholipids and proteins on plasma membranes. Migraine is a primary headache disorder which has growing evidences of autoimmune-mediated pathogenesis and previous studies suggested the presence of aPLs in migraine patients. AIMS: To evaluate the comorbid association between aPLs (aCL, anti-β2GPI and LA) and migraine compared to healthy controls...
March 6, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28278279/toll-like-receptor-9-suppresses-lupus-disease-in-fas-sufficient-mrl-mice
#7
Kevin M Nickerson, Yujuan Wang, Sheldon Bastacky, Mark J Shlomchik
Genetic deficiency in TLR9 accelerates pathogenesis in the spontaneous polygenic MRL.Faslpr murine model of systemic lupus erythematosus, despite the absence of anti-nucleosome autoantibodies. However, it could be argued that this result was dependent on Fas-deficiency rather than lupus-promoting genes in the MRL genetic background. Here we report the effects of TLR9 deficiency on autoimmune disease independent of the lpr mutation in Fas by characterizing Tlr9-/- and Tlr9+/+ mice on the Fas-intact MRL/+ genetic background...
2017: PloS One
https://www.readbyqxmd.com/read/28275260/beyond-tnf-tnf-superfamily-cytokines-as-targets-for-the-treatment-of-rheumatic-diseases
#8
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...
March 9, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28274696/expanding-the-b-cell-centric-view-of-systemic-lupus-erythematosus
#9
REVIEW
Peter A Morawski, Silvia Bolland
Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by a breakdown of self-tolerance in B cells and the production of antibodies against nuclear self-antigens. Increasing evidence supports the notion that additional cellular contributors beyond B cells are important for lupus pathogenesis. In this review we consider recent advances regarding both the pathogenic and the regulatory role of lymphocytes in SLE beyond the production of IgG autoantibodies. We also discuss various inflammatory effector cell types involved in cytokine production, removal of self-antigens, and responses to autoreactive IgE antibodies...
March 5, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28274252/elevated-serum-autoantibodies-against-co-inhibitory-pd-1-facilitate-t-cell-proliferation-and-correlate-with-disease-activity-in-new-onset-systemic-lupus-erythematosus-patients
#10
Hui Shi, Junna Ye, Jialin Teng, Yufeng Yin, Qiongyi Hu, Xinyao Wu, Honglei Liu, Xiaobing Cheng, Yutong Su, Mengru Liu, Juanfang Gu, Ting Lu, HaoJie Chen, Hui Zheng, Yue Sun, Chengde Yang
BACKGROUND: Programmed cell death protein 1 (PD-1) plays an important role in immune response regulation as a co-inhibitory signal during T cell activation. However, there is little known about the serum autoantibody profile of PD-1 in systemic lupus erythematosus (SLE), a disease characterized by the breakdown of immune tolerance to self-antigens and an excessive production of autoantibodies. Thus, we aim to investigate the serum levels and function of anti-PD-1 in patients with new-onset SLE...
March 9, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28263097/transcriptional-and-epigenetic-regulation-of-follicular-t-helper-cells-and-their-role-in-autoimmunity
#11
Hong Qiu, Haijing Wu, Vera Chan, Chak-Sing Lau, Qianjin Lu
T-follicular helper (Tfh) cells are a specialized subset of T cells that provide help to B cells and promote the formation of germinal centers (GCs). Tfh cells transmit important signals to B cells that drive class switch recombination, somatic hyper-mutation, the generation of high-affinity antibodies, immunological memory and their differentiation into plasma cells or memory B cells in the GCs. Tfh-cell differentiation is regulated by the coordinated functions of distinct cytokines, including interleukin (IL)-6, IL-21, IL-12, IL-23, IL-2, IL-7 and transforming growth factor-β (TGF-β), as well as transcription factors, including B-cell lymphoma 6 protein (Bcl-6), Signal transducers and activators of transcription (STAT)1, STAT3, STAT4, B-cell activating transcription factor (Batf), interferon regulatory factor 4 (IRF4), v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (C-Maf), T-cell-specific transcription factor 1 (TCF-1) and Achaete-scute homolog 2 (Acl2), which have been shown to form a complex transcriptional network...
March 2017: Autoimmunity
https://www.readbyqxmd.com/read/28262211/complement-alternative-pathway-s-activation-in-patients-with-lupus-nephritis
#12
Di Song, Wei-Yi Guo, Feng-Mei Wang, Yong-Zhe Li, Yan Song, Feng Yu, Ming-Hui Zhao
OBJECTIVE: The aim of this study was to detect the spectrum of complement activation pathways in circulation and to assess their correlations with clinical and pathologic features in a large lupus nephritis cohort from China. MATERIALS AND METHODS: Plasma levels of C1q, mannose-binding lectin, C4d, Bb, C3, C3a, C5a and soluble C5b-9 were detected by enzyme-linked immunosorbent assay in 222 patients with active biopsy-proven lupus nephritis, 34 patients with lupus nephritis at remission, 82 patients with active systemic lupus erythematosus without renal involvement and 39 normal controls...
March 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28258497/treatment-of-pediatric-onset-lupus-nephritis-a-proposal-of-optimal-therapy
#13
REVIEW
Hiroshi Tanaka, Kensuke Joh, Tadaatsu Imaizumi
Lupus nephritis (LN) is one of the major clinical manifestations of systemic lupus erythematosus (SLE) which occurs frequently in the early stages of pediatric-onset cases. Since SLE is a chronic disease associated with frequent disease flares and effective and safe maintenance therapy is required for achieving a favorable outcome, optimal treatment for LN in pubertal patients is a great challenge that remains to be overcome. Although its etiology remains unclear, it has been reported that the innate and adaptive immune systems have been reported to play an important role in the pathogenesis of SLE...
March 3, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28258054/thrombophilia-risk-is-not-increased-in-children-after-perinatal-stroke
#14
Colleen Curtis, Aleksandra Mineyko, Patricia Massicotte, Michael Leaker, Xiu Yan Jiang, Amalia Floer, Adam Kirton
Perinatal stroke causes cerebral palsy and lifelong disability. Specific diseases are definable but mechanisms are poorly understood. Evidence suggests possible associations between arterial perinatal stroke and prothrombotic disorders but population-based, controlled, disease-specific studies are limited. Understanding thrombophilia in perinatal stroke informs pathogenesis models and clinical management. We conducted a population-based, prospective, case-control study to determine the association of specific perinatal stroke diseases with known thrombophilias...
March 3, 2017: Blood
https://www.readbyqxmd.com/read/28257596/interferon-%C3%AE-coincides-with-suppressed-levels-of-pentraxin-3-ptx3-in-systemic-lupus-erythematosus-and-regulates-leukocyte-ptx3-in-vitro
#15
Lina Wirestam, Helena Enocsson, Thomas Skogh, Maija-Leena Eloranta, Lars Rönnblom, Christopher Sjöwall, Jonas Wetterö
Dysfunctional elimination of cell debris, and the role of opsonins such as pentraxins, is of interest regarding systemic lupus erythematosus (SLE) pathogenesis. Interferon-α (IFN-α) is typically elevated during SLE flares, and inhibits hepatocyte production of the pentraxin 'C-reactive protein' (CRP), partly explaining the poor correlation between CRP levels and SLE disease activity. The extrahepatically produced 'pentraxin 3' (PTX3) shares waste disposal functions with CRP, but has not been extensively studied in SLE...
March 3, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28244652/association-of-leptin-and-leptin-receptor-gene-polymorphisms-with-systemic-lupus-erythematosus-in-a-chinese-population
#16
Hong-Miao Li, Tian-Ping Zhang, Rui-Xue Leng, Xiang-Pei Li, De-Guang Wang, Xiao-Mei Li, Dong-Qing Ye, Hai-Feng Pan
To explore the association of LEP and leptin receptor (LEPR) gene single-nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. Four LEP SNPs (rs11761556, rs12706832, rs2071045 and rs2167270) and nine LEPR SNPs (rs10749754, rs1137100, rs1137101, rs13306519, rs8179183, rs1805096, rs3790434, rs3806318 and rs7518632) were genotyped in a cohort of 633 patients with SLE and 559 healthy controls. Genotyping of SNPs was performed with improved multiple ligase detection reaction (iMLDR)...
February 28, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28242635/immunosuppression-with-mycophenolate-mofetil-attenuates-hypertension-in-an-experimental-model-of-autoimmune-disease
#17
Erin B Taylor, Michael J Ryan
BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that predominantly affects women and is associated with prevalent hypertension, renal injury, and cardiovascular disease. Immune system dysfunction is recognized as an important factor in the pathogenesis of hypertension. We recently showed that preventing autoimmunity prevents the development of hypertension in an experimental model of SLE (female NZBWF1 mice). The present study tests the hypothesis that mycophenolate mofetil (MMF), an immunosuppressive therapy used clinically to treat SLE by depleting proliferating B and T lymphocytes, can improve blood pressure control...
February 27, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28239656/autoreactive-helper-t-cells-alleviate-the-need-for-intrinsic-tlr-signaling-in-autoreactive-b-cell-activation
#18
Josephine R Giles, Adriana Turqueti Neves, Ann Marshak-Rothstein, Mark J Shlomchik
T cells play a significant role in the pathogenesis of systemic autoimmune diseases, including systemic lupus erythematosus; however, there is relatively little information on the nature and specificity of autoreactive T cells. Identifying such cells has been technically difficult because they are likely to be rare and low affinity. Here, we report a method for identifying autoreactive T cell clones that recognize proteins contained in autoantibody immune complexes, providing direct evidence that functional autoreactive helper T cells exist in the periphery of normal mice...
February 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28219888/cd74-deficiency-mitigates-systemic-lupus-erythematosus-like-autoimmunity-and-pathological-findings-in-mice
#19
Yi Zhou, Huimei Chen, Li Liu, Xueqing Yu, Galina K Sukhova, Min Yang, Lijun Zhang, Vasileios C Kyttaris, George C Tsokos, Isaac E Stillman, Takaharu Ichimura, Joseph V Bonventre, Peter Libby, Guo-Ping Shi
CD74 mediates MHC class-II antigenic peptide loading and presentation and plays an important role in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus. C57BL/6 Fas(lpr) mice that develop spontaneous lupus-like autoimmunity and pathology showed elevated CD74 expression in the inflammatory cell infiltrates and the adjacent tubular epithelial cells (TECs) in kidneys affected by lupus nephritis but negligible levels in kidneys from age-matched wild-type mice. The inflammatory cytokine IFN-γ or IL-6 induced CD74 expression in kidney TECs in vitro...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28219887/disruption-of-pathogenic-cellular-networks-by-il-21-blockade-leads-to-disease-amelioration-in-murine-lupus
#20
Jin-Young Choi, Abhinav Seth, Michael Kashgarian, Sonia Terrillon, Emma Fung, Lili Huang, Li Chun Wang, Joe Craft
Systemic lupus erythematosus (lupus) is characterized by autoantibody-mediated organ injury. Follicular Th (Tfh) cells orchestrate physiological germinal center (GC) B cell responses, whereas in lupus they promote aberrant GC responses with autoreactive memory B cell development and plasma cell-derived autoantibody production. IL-21, a Tfh cell-derived cytokine, provides instructional cues for GC B cell maturation, with disruption of IL-21 signaling representing a potential therapeutic strategy for autoantibody-driven diseases such as systemic lupus erythematosus...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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