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SLE AND T cells

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https://www.readbyqxmd.com/read/29150407/disease-trends-over-time-and-cd4-ccr5-t-cells-expansion-predict-carotid-atherosclerosis-development-in-patients-with-systemic-lupus-erythematosus
#1
A Baragetti, G A Ramirez, M Magnoni, K Garlaschelli, L Grigore, M Berteotti, I Scotti, E Bozzolo, A Berti, P G Camici, A L Catapano, A A Manfredi, E Ammirati, G D Norata
BACKGROUND AND AIM: Patients with Systemic Lupus Erythematosus (SLE) present increased cardiovascular mortality compared to the general population. Few studies have assessed the long-term development and progression of carotid atherosclerotic plaque in SLE patients. Our aim was to investigate the association of clinical and laboratory markers of disease activity and classical cardiovascular risk factors (CVRF) with carotid atherosclerosis development in SLE patients in a prospective 5-year study...
September 18, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/29145701/tnf-antagonists-killing-two-birds-with-one-biologic-stone
#2
EDITORIAL
Joan M Bathon, Jon T Giles, Daniel H Solomon
Forty years have passed since it was first recognized that patients with autoimmune rheumatic disease have an increased risk of fatal and non-fatal cardiovascular (CV) events (1) Although initial reports focused on rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), similar findings were verified subsequently in patients with psoriasis (Ps) and/or psoriatic arthritis (PsA) and spondyloarthritis. An early feature of the atherosclerotic lesion is infiltration with inflammatory cells, particularly monocytes/macrophages, and the presence of these cells in mature plaque elevates the risk of plaque rupture and thrombosis (2)...
November 16, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29145159/potential-link-between-m-6-a-modification-and-systemic-lupus-erythematosus
#3
REVIEW
Lian-Ju Li, Yin-Guang Fan, Rui-Xue Leng, Hai-Feng Pan, Dong-Qing Ye
The field of m(6)A modification and epitranscriptomics has recently attracted much attention. More methods allowing for precise m(6)A site profiling and location are developed and crucial players of m(6)A modification machinery are increasingly identified. Although some challenges remain, m(6)A modification is found to modulate almost all aspects of RNA metabolism, such as splicing, stability, structure, translation, and export. Thus, m(6)A modification adds a new layer of post-transcriptional gene expression regulation, and it is implicated in T cell response to HIV infection, type I interferon production, and T cell differentiation and homeostasis...
November 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29141242/chloroquine-autophagic-inhibition-rebalances-th17-treg-mediated-immunity-and-ameliorates-systemic-lupus-erythematosus
#4
Ning An, Yanwen Chen, Chao Wang, Chen Yang, Zhi-Hong Wu, Jing Xue, Lin Ye, Shujun Wang, Hua-Feng Liu, Qingjun Pan
BACKGROUND: Imbalanced cellular immunity is critical to the pathogenesis of systemic lupus erythematosus (SLE). Recently, autophagy has emerged as a key homeostatic mechanism in T lymphocytes. This study was conducted to explore the impact of autophagy on the Th17/ regulatory T (Treg) immune imbalance in SLE. METHODS: Peripheral Th17 and Treg cells from newly diagnosed patients with SLE and healthy controls were detected by flow cytometry. Additionally, the effects of chloroquine (CQ) autophagic inhibition on the Th17/Treg immune response were investigated in vitro...
November 14, 2017: Cellular Physiology and Biochemistry
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
#5
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/29113828/downregulation-of-bdh2-modulates-iron-homeostasis-and-promotes-dna-demethylation-in-cd4-t-cells-of-systemic-lupus-erythematosus
#6
Ming Zhao, Meng-Ying Li, Xiao-Fei Gao, Su-Jie Jia, Ke-Qin Gao, Yin Zhou, Hui-Hui Zhang, Yi Huang, Jing Wang, Hai-Jing Wu, Qian-Jin Lu
DNA hypomethylation plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). Here we investigated whether 3-hydroxy butyrate dehydrogenase 2 (BDH2), a modulator of intracellular iron homeostasis, was involved in regulating DNA hypomethylation and hyper-hydroxymethylation in lupus CD4(+) T cells. Our results showed that BDH2 expression was decreased, intracellular iron was increased, global DNA hydroxymethylation level was elevated, while methylation level was reduced in lupus CD4(+) T cells compared with healthy controls...
November 4, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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
#7
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/29108826/physical-activity-and-autoimmune-diseases-get-moving-and-manage-the-disease
#8
REVIEW
Kassem Sharif, Abdulla Watad, Nicola Luigi Bragazzi, Micheal Lichtbroun, Howard Amital, Yehuda Shoenfeld
Physical activity, by definition, is any skeletal muscle body movement that results in energy expenditure. In the last few decades, a plethora of scientific evidences have accumulated and confirmed the beneficial role of physical activity as a modifiable risk factor for a wide variety of chronic diseases including cardiovascular diseases (CVDs), diabetes mellitus and cancer, among others. Autoimmune diseases are a heterogeneous group of chronic diseases, which occur secondary to loss of self-antigen tolerance...
November 3, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29074827/-update-on-recent-progress-in-vitamin-d-research-the-effects-of-vitamin-d-in-autoinflammatory-diseases
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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/29038617/patients-with-systemic-lupus-erythematosus-show-increased-levels-and-defective-function-of-cd69-t-regulatory-cells
#15
Marlen Vitales-Noyola, Brenda Oceguera-Maldonado, Perla Niño-Moreno, Nubia Baltazar-Benítez, Lourdes Baranda, Esther Layseca-Espinosa, Carlos Abud-Mendoza, Roberto González-Amaro
T regulatory (Treg) cells have a key role in the pathogenesis of chronic inflammatory and autoimmune diseases. A CD4(+)CD69(+) T cell subset has been described that behaves as Treg lymphocytes, exerting an important immune suppressive effect. In this study, we analyzed the levels and function of CD4(+)CD69(+) Treg cells in patients with systemic lupus erythematosus (SLE). Blood samples were obtained from 22 patients with SLE and 25 healthy subjects. Levels of CD4(+)CD69(+) Treg cells were analyzed by multiparametric flow cytometry, and their function was measured by an assay of suppression of lymphocyte activation and through the inhibition of cytokine synthesis...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/29031579/cd4-cd52-lo-t-cell-expression-contributes-to-the-development-of-systemic-lupus-erythematosus
#16
Masataka Umeda, Tomohiro Koga, Kunihiro Ichinose, Takashi Igawa, Tomohito Sato, Ayuko Takatani, Toshimasa Shimizu, Shoichi Fukui, Ayako Nishino, Yoshiro Horai, Yasuko Hirai, Shin-Ya Kawashiri, Naoki Iwamoto, Toshiyuki Aramaki, Mami Tamai, Hideki Nakamura, Kazuo Yamamoto, Norio Abiru, Tomoki Origuchi, Yukitaka Ueki, Atsushi Kawakami
The cell-surface glycoprotein CD52 is widely expressed in lymphocytes. CD4(+)CD52(hi) T cells are functioning suppressor CD4(+)T cells. We investigated the role of the immune regulation of CD4(+)CD52 T cells in systemic lupus erythematosus (SLE). CD4(+)CD52(lo) T cells were increased in SLE patients, in positive correlation with SLEDAI, anti-ds-DNA antibody, and IgG concentration. Circulating follicular helper-like T cells (Tfh-like cells) were also increased in SLE, in positive correlation with CD4(+)CD52(lo) T cells...
October 13, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29023682/short-term-cytokine-stimulation-reveals-regulatory-t%C3%A2-cells-with-down-regulated-foxp3-expression-in-human-peripheral-blood
#17
Paula Tabares, Susanne Berr, Daniela Langenhorst, Birgit Sawitzki, Ineke Ten Berge, Hans-Peter Tony, Thomas Hünig
The identification of regulatory T cells (Treg cells) in human peripheral blood is an important tool in diagnosis, research, and therapeutic intervention. As compared to lymphoid tissues, the frequencies of circulating Treg cells identified as CD4(+) CD25(+) Foxp3(+) are, however, low. We here show that many of these cells remain undetected due to transient down regulation of Foxp3, which rapidly decays in the absence of cytokine-mediated STAT5 signals. Short-term incubation of PBMCs or isolated CD4(+) T cells, but not of lymph node cells, with IL-2, -7, or -15 more than doubles the frequency of Foxp3(+) CD25(+) among CD4(+) T cells detectable by flow cytometry...
October 11, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29021794/cd95-fas-non-apoptotic-signaling-pathways-and-kinases
#18
REVIEW
Matthieu Le Gallo, Amanda Poissonnier, Patrick Blanco, Patrick Legembre
Endothelial cells lining new blood vessels that develop during inflammatory disorders or cancers act as doors that either allow or block access to the tumor or inflamed organ. Recent data show that these endothelial cells in cancer tissues and inflamed tissues of lupus patients overexpress CD95L, the biological role of which is a subject of debate. The receptor CD95 (also named Fas or apoptosis antigen 1) belongs to the tumor necrosis factor (TNF) receptor superfamily. Its cognate ligand, CD95L, is implicated in immune homeostasis and immune surveillance...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29021537/elevated-levels-of-ccr6-t-helper-22-cells-correlate-with-skin-and-renal-impairment-in-systemic-lupus-erythematosus
#19
Wei Zhong, Yanfang Jiang, Hongshuang Ma, Jiang Wu, Zhenyu Jiang, Ling Zhao
Systemic lupus erythematosus (SLE) is an autoimmune disease with a variety of pathological features. Our study investigated the potential role of CCR6(+) T cells in organ impairment of SLE patients. We analyzed CCR6(+/-) T cell subset populations and compared the concentrations of IL-22, IFN-γ, TNF-α, and IL-17A cytokines in 67 patients with newly diagnosed SLE and 26 healthy controls. We found that SLE patients had elevated percentages of CCR6(+) T, CCR6(+) Th22, Th17, Th17.1, and CCR6(-) Th2 cell subsets, along with increased concentrations of IL-22, IFN-γ, TNF-α, and IL-17 cytokines...
October 11, 2017: Scientific Reports
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
#20
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
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