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nk cells AND sle

Devika Gupta, Supreet Mohanty, Deepshi Thakral, Arvind Bagga, Naveet Wig, Dipendra Kumar Mitra
BACKGROUND Hemophagocytic lymphohistiocytosis (HLH) in the background of systemic lupus erythematosus (SLE) is rare. Inability to discriminate between these two entities may be fatal for the patient. Here we report two cases of SLE with secondary HLH, one of which manifested HLH as the initial presentation, and the significance of HLH's timely diagnosis. CASE REPORT We describe two cases of SLE secondarily affected by HLH, which were diagnosed by various laboratory parameters and detection of profoundly reduced NK cell activity by using flow cytometry...
October 13, 2016: American Journal of Case Reports
Mikhail Olferiev, Elzbieta Jacek, Kyriakos A Kirou, Mary K Crow
To gain novel insights into the immunopathogenesis of systemic lupus erythematosus we have analyzed gene expression data from isolated CD4(+) T cells, CD8(+) T cells, CD19(+) B cells, and CD56(+) NK-cell enriched peripheral blood cell fractions from patients and healthy donors. As predicted, type I interferon-inducible gene transcripts are overexpressed in all populations. Transcripts preferentially expressed in SLE CD4(+) and CD8(+) T cells include those associated with Tregulatory and Th17 effector cell programs, respectively, but in each case additional transcripts predicted to limit differentiation of those effector cells are detected...
August 26, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
S Psarelis, E Nikiphorou
No abstract text is available yet for this article.
July 20, 2016: Lupus
Sahar Mortezagholi, Zohreh Babaloo, Parisa Rahimzadeh, Mojgan Ghaedi, Hayedeh Namdari, Shirin Assar, Maryam Azimi Mohamadabadi, Eisa Salehi
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which results in damage to various organs. Some animal studies have revealed that activation of Toll-like receptors (TLRs) is important in the pathogenesis of SLE. In the present study, the percentage of different immune cell subsets in 35 SLE patients and 38 control subjects was analyzed by flow cytometry. We also assessed the expression of TLR9 in the population of peripheral blood mononuclear cells (PBMCs) including T lymphocytes (CD4+ and CD8+), B lymphocytes (CD19+), NK cells (CD56+) and monocytes (CD14+) in SLE patients and healthy controls...
June 2016: Iranian Journal of Allergy, Asthma, and Immunology
A L Roberts, B G Fürnrohr, T J Vyse, B Rhodes
Complement receptor 3 (CR3, CD11b/CD18) is a multi-functional receptor expressed predominantly on myeloid and natural killer (NK) cells. The R77H variant of CD11b, encoded by the ITGAM rs1143679 polymorphism, is associated robustly with development of the autoimmune disease systemic lupus erythematosus (SLE) and impairs CR3 function, including its regulatory role on monocyte immune signalling. The role of CR3 in NK cell function is unknown. Leukadherin-1 is a specific small-molecule CR3 agonist that has shown therapeutic promise in animal models of vascular injury and inflammation...
September 2016: Clinical and Experimental Immunology
M Akhtari, A Farazmand, M Mahmoudi, M Akbarian, N Ahmadzadeh, Z Mirkazemi, S Mostafaei, A R Jamshidi
OBJECTIVE: Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease. Natural killer (NK) cells play a critical role in the pathogenesis of autoimmune disorders that mainly express killer cell immunoglobulin-like receptors (KIRs). The present study was undertaken to determine the association of the KIR alleles, genotypes, and KIR-human leukocyte antigen (HLA) ligand gene combinations with the susceptibility to SLE. METHODS: The genotyping of 17 KIR and 5 HLA loci was performed using the polymerase chain reaction-sequence specific primer (PCR-SSP) method...
October 2016: Lupus
Yuriy Baglaenko, Kieran P Manion, Nan-Hua Chang, Eric Gracey, Christina Loh, Joan E Wither
The development and progression of systemic lupus erythematosus is mediated by the complex interaction of genetic and environmental factors. To decipher the genetics that contribute to pathogenesis and the production of pathogenic autoantibodies, our lab has focused on the generation of congenic lupus-prone mice derived from the New Zealand Black (NZB) strain. Previous work has shown that an NZB-derived chromosome 4 interval spanning 32 to 151 Mb led to expansion of CD5+ B and Natural Killer T (NKT) cells, and could suppress autoimmunity when crossed with a lupus-prone mouse strain...
2016: PloS One
M Olde Bekkink, Y M Ahmed-Ousenkova, M G Netea, W J van der Velden, J H Berden
Among patients with systemic lupus erythematosus (SLE) there is an increased risk of haematological malignancies, especially non-Hodgkin lymphoma. However, the association of SLE with aggressive CD3 negative natural killer (NK)-cell leukaemia has not been reported so far. We present a case of a 39-year-old woman with SLE, aggressive NK-cell leukaemia and tuberous sclerosis complex. The prior probability of developing the combination of these three rare diseases by coincidence is extremely low (<10(-13))...
June 2016: Lupus
Christina Dillmann, Christian Ringel, Julia Ringleb, Javier Mora, Catherine Olesch, Annika F Fink, Edward Roberts, Bernhard Brüne, Andreas Weigert
Plasmacytoid dendritic cells (pDCs) produce large amounts of type I IFN in response to TLR7/9 ligands. This conveys antiviral effects, activates other immune cells (NK cells, conventional DCs, B, and T cells), and causes the induction and expansion of a strong inflammatory response. pDCs are key players in various type I IFN-driven autoimmune diseases such as systemic lupus erythematosus or psoriasis, but pDCs are also involved in (anti-)tumor immunity. The sphingolipid sphingosine-1-phosphate (S1P) signals through five G-protein-coupled receptors (S1PR1-5) to regulate, among other activities, immune cell migration and activation...
February 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Niels H H Heegaard, Anting Liu Carlsen, Kerstin Skovgaard, Peter M H Heegaard
MicroRNAs (miRNAs) are differentially regulated in healthy, activated, inflamed, neoplastic, or otherwise pathological cells and tissues. While their main functions are executed intracellularly, many miRNAs can reproducibly be detected extracellularly in plasma and serum. This circulating, extracellular miRNA is protected against degradation by complexation with carrier proteins and/or by being enclosed in subcellular membrane vesicles. This, together with their tissue- and disease-specific expression, has fuelled the interest in using circulating microRNA profiles as harbingers of disease, i...
2015: EXS
Yi-Lung Lin, Shih-Chang Lin
Expressed on the cell surface of most of NK cells and some T cells, CD161 has been shown to deliver inhibitory signal in human NK cells. To determine whether the CD161-expressing cell quantities and the cell surface expression levels of CD161 in NK and T cells were altered in systemic lupus erythematosus (SLE) patients, we analyzed the CD3, CD56 and CD161 expression patterns of peripheral blood lymphocytes by flow cytometric analysis to identify different NK and T cell subpopulations. The cell surface expression levels of CD161 were estimated by the mean florescence intensities (MFIs) of CD161...
November 21, 2015: Clinical and Experimental Medicine
Jun Wu, Yifei Cheng, Leping Zhang
This retrospective single-center study assessed the incidence and clinical features of immune manifestations of refractory cytopenia of childhood (RCC) and childhood aplastic anemia (AA). We evaluated 72 children with RCC and 123 with AA between February 2008 and March 2013. RCC was associated with autoimmune disease in 4 children, including 1 case each with autoimmune hemolytic anemia, rheumatoid arthritis, systemic lupus erythematosus, and anaphylactoid purpura. No children with AA were diagnosed with autoimmune diseases...
December 2015: Leukemia Research
Takeharu Minamitani, Teruhito Yasui, Yijie Ma, Hufeng Zhou, Daisuke Okuzaki, Chiau-Yuang Tsai, Shuhei Sakakibara, Benjamin E Gewurz, Elliott Kieff, Hitoshi Kikutani
Epstein-Barr virus (EBV) infects germinal center (GC) B cells and establishes persistent infection in memory B cells. EBV-infected B cells can cause B-cell malignancies in humans with T- or natural killer-cell deficiency. We now find that EBV-encoded latent membrane protein 2A (LMP2A) mimics B-cell antigen receptor (BCR) signaling in murine GC B cells, causing altered humoral immune responses and autoimmune diseases. Investigation of the impact of LMP2A on B-cell differentiation in mice that conditionally express LMP2A in GC B cells or all B-lineage cells found LMP2A expression enhanced not only BCR signals but also plasma cell differentiation in vitro and in vivo...
September 15, 2015: Proceedings of the National Academy of Sciences of the United States of America
William Stohl, Joan T Merrill, R John Looney, Jill Buyon, Daniel J Wallace, Michael H Weisman, Ellen M Ginzler, Blaire Cooke, Donna Holloway, Arunan Kaliyaperumal, Kameswara Rao Kuchimanchi, Tsui Chern Cheah, Erik Rasmussen, John Ferbas, Shelley S Belouski, Wayne Tsuji, Debra J Zack
INTRODUCTION: Blisibimod is a potent B cell-activating factor (BAFF) antagonist that binds to both cell membrane-expressed and soluble BAFF. The goal of these first-in-human studies was to characterize the safety, tolerability, and pharmacokinetic and pharmacodynamic profiles of blisibimod in subjects with systemic lupus erythematosus (SLE). METHODS: SLE subjects with mild disease that was stable/inactive at baseline received either a single dose of blisibimod (0...
2015: Arthritis Research & Therapy
Arun Kumar, Maria F Perdomo, Anu Kantele, Lea Hedman, Klaus Hedman, Rauli Franssila
A novel conception of CD4(+) T cells with cytolytic potential (CD4(+) CTL) is emerging. These cells appear to have a part in controlling malignancies and chronic infections. Human parvovirus B19 can cause a persistent infection, yet no data exist on the presence of B19-specific CD4(+) CTLs. Such cells could have a role in the pathogenesis of some autoimmune disorders reported to be associated with B19. We explored the cytolytic potential of human parvovirus B19-specific T cells by stimulating peripheral blood mononuclear cell (PBMC) with recombinant B19-VP2 virus-like particles...
July 2015: Clinical & Translational Immunology
Roberto Spada, José M Rojas, Domingo F Barber
Systemic lupus erythematosus is a chronic, multifactorial autoimmune disease of complex etiology, characterized by loss of tolerance to nuclear autoantigens, expansion of autoreactive T and B cell clones, polyclonal B cell activation that gives rise to hypergammaglobulinemia, and increased autoantibody production, as well as immune complex deposition and multiorgan tissue inflammation. As disease progresses, immune cells, mainly T cells and macrophages, infiltrate affected organs and amplify the local inflammatory response...
October 2015: Journal of Leukocyte Biology
Tue Kruse Rasmussen, Thomas Andersen, Rasmus Otkjær Bak, Gloria Yiu, Christian Møller Sørensen, Kristian Stengaard-Pedersen, Jacob Giehm Mikkelsen, Paul Joseph Utz, Christian Kanstrup Holm, Bent Deleuran
INTRODUCTION: Interleukin (IL)-21 is a key cytokine in autoimmune diseases such as systemic lupus erythematosus (SLE) by its regulation of autoantibody production and inflammatory responses. The objective of this study is to investigate the signaling capacity of IL-21 in T and B cells and assess its possible regulation by microRNA (miR)-155 and its target gene suppressor of cytokine signaling 1 (SOCS1) in SLE. METHODS: The signaling capacity of IL-21 was quantified by stimulating peripheral blood mononuclear cells (PBMCs) with IL-21 and measuring phosphorylation of STAT3 (pSTAT3) in CD4+ T cells, B cells, and natural killer cells...
2015: Arthritis Research & Therapy
William E O'Gorman, Elena W Y Hsieh, Erica S Savig, Pier Federico Gherardini, Joseph D Hernandez, Leo Hansmann, Imelda M Balboni, Paul J Utz, Sean C Bendall, Wendy J Fantl, David B Lewis, Garry P Nolan, Mark M Davis
BACKGROUND: Activation of Toll-like receptors (TLRs) induces inflammatory responses involved in immunity to pathogens and autoimmune pathogenesis, such as in patients with systemic lupus erythematosus (SLE). Although TLRs are differentially expressed across the immune system, a comprehensive analysis of how multiple immune cell subsets respond in a system-wide manner has not been described. OBJECTIVE: We sought to characterize TLR activation across multiple immune cell subsets and subjects, with the goal of establishing a reference framework against which to compare pathologic processes...
November 2015: Journal of Allergy and Clinical Immunology
Y Baglaenko, K P Manion, N-H Chang, C Loh, G Lajoie, J E Wither
Systemic lupus erythematosus is a complex autoimmune disorder characterized by the production of pathogenic anti-nuclear antibodies. Previous work from our laboratory has shown that the introgression of a New Zealand Black-derived chromosome 4 interval onto a lupus-prone background suppresses the disease. Interestingly, the same genetic interval promoted the expansion of both Natural Killer T- and CD5(+) B cells in suppressed mice. In this study, we show that ablation of NKT cells with a CD1d knockout had no impact on either the suppression of lupus or the expansion of CD5(+) B cells...
July 2015: Genes and Immunity
Fei Liu, Hongye Fan, Deshan Ren, Guanjun Dong, Erling Hu, Jianjian Ji, Yayi Hou
B cells present lipid antigens to CD1d-restricted invariant natural killer T (iNKT) cells to maintain autoimmune tolerance, and this process is disrupted in systemic lupus erythematosus (SLE). Inflammation may inhibit CD1d expression to exacerbate the pathology of lupus. However, how inflammation regulates CD1d expression on B cells is unclear in SLE. In the present study, we showed that the surface expression of CD1d on B cells from SLE mice was decreased and that stimulation of inflammatory responses through TLR9 decreased the membrane and total CD1d levels of CD1d on B cells...
July 2015: European Journal of Immunology
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