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NK cell AND systemic lupus erythematosus

Denis Comte, Maria P Karampetsou, Nobuya Yoshida, Katalin Kis-Toth, Vasileios C Kyttaris, George C Tsokos
OBJECTIVE: Effector CD8+ T cell function is impaired in SLE and associated with compromised ability to fight infections. SLAMF7 engagement has been shown to enhance NK cell degranulation. Thus, we characterized the expression and function of SLAMF7 on CD8+ T cells subsets isolated from peripheral blood of SLE patients and healthy subjects. METHODS: CD8+ T cell subset distribution, SLAMF7 expression and cytolytic enzyme expression (perforin, GzmA, GzmB) were monitored on cells isolated from SLE patients and healthy controls by flow cytometry...
January 11, 2017: Arthritis & Rheumatology
Syh-Jae Lin, Ji-Yih Chen, Ming-Ling Kuo, Hsiu-Shan Hsiao, Pei-Tzu Lee, Jing-Long Huang
Adhesion molecules may play an important role in systemic lupus erythematosus (SLE) pathogenesis. We investigated the effect of interleukin- (IL-) 15 on CD11b, CD54, and CD62L expression on natural killer (NK) cells, T cells, and CD56(+)CD3(+) NKT-like cells from SLE subjects and healthy controls. SLE patients had decreased circulating NK cells and NKT-like cells compared to controls. NK cells from SLE patients showed higher CD11b and CD62L expression compared to controls. IL-15 enhanced CD11b and CD54 but downregulated CD62L expression on NK cells from SLE patients...
2016: Mediators of Inflammation
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...
November 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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
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
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...
February 2017: Clinical and Experimental Medicine
Johannes Nossent, Sue Lester, Maureen Rischmueller, Peter Zalewski
BACKGROUND: Zn (Zn) is an essential trace element with important roles in protein structure and function. Labile Zn is the fraction available for regulatory functions through it loose binding to albumin. As Zn deprivation reduces labile Zn levels and leads to an immune compromised state, we investigated labile Zn levels in the context of systemic autoimmune disease. METHODS: Cross sectional case control study in patients with Systemic Lupus Erythematosus (SLE; n= 45), primary Sjögren's Syndrome (n= 53) and healthy controls (HC; n= 27)...
October 26, 2015: Current Rheumatology Reviews
Katalin Kis-Toth, Denis Comte, Maria P Karampetsou, Vasileios C Kyttaris, Lakshmi Kannan, Cox Terhorst, George C Tsokos
OBJECTIVE: Engagement of signaling lymphocytic activation molecule family member 4 (SLAMF4; CD244, 2B4) by its ligand SLAMF2 (CD48) modulates the function and expansion of both natural killer cells and a subset of cytotoxic CD8+ T cells. Because the cytotoxicity of CD8+ T lymphocytes isolated from patients with systemic lupus erythematosus (SLE) is known to be impaired, the aim of this study was to assess whether the expression and function of the checkpoint regulator SLAMF4 are altered on CD8+ T cells from patients with SLE...
January 2016: Arthritis & Rheumatology
Xiao-Lei Huang, Li Zhang, Jian-Ping Li, Yu-Jie Wang, Yu Duan, Jing Wang
MicroRNAs (miRNAs) are short non-coding RNAs that play an important role in post-transcriptional regulation of gene expression. The past studies showed that miR-150 might emerge as a master regulator of gene expression during the immune cells differentiation and immune response process. Its regulation ability in immune cellular process might contribute to the host defense against invading pathogens, and dysregulated expression of miR-150 in immune cells might result in autoimmune diseases. This review summarized that miR-150 could regulate B cells, T cells and NK/iNKT cells differentiation and immune response...
2015: Autoimmunity
Xiao-Lei Huang, Li Zhang, Jian-Ping Li, Yu-Jie Wang, Yu Duan, Jing Wang
MicroRNAs (miRNAs) are short non-coding RNAs that play an important role in post-transcriptional regulation of gene expression. The past studies showed that miR-150 might emerge as a master regulator of gene expression during the immune cells differentiation and immune response process. Its regulation ability in immune cellular process might contribute to the host defense against invading pathogens, and dysregulated expression of miR-150 in immune cells might result in autoimmune diseases. This review summarized that miR-150 could regulate B cells, T cells and NK/iNKT cells differentiation and immune response...
August 14, 2015: Autoimmunity
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
Bianca Tesi, Samuel C C Chiang, Dalia El-Ghoneimy, Ayad Ahmed Hussein, Cecilia Langenskiöld, Rabia Wali, Zehra Fadoo, João Pinho Silva, Ramón Lecumberri, Sule Unal, Magnus Nordenskjöld, Yenan T Bryceson, Jan-Inge Henter, Marie Meeths
BACKGROUND: Perforin, encoded by PRF1, is a pore-forming protein crucial for lymphocyte cytotoxicity. Biallelic PRF1 nonsense mutations invariably result in early-onset hemophagocytic lymphohistiocytosis (HLH), termed familial HLH type 2 (FHL2). In contrast, biallelic PRF1 missense mutations may give rise to later-onset disease and more variable manifestations. PROCEDURE: We retrospectively searched our database for patients from families with siblings carrying biallelic PRF1 missense mutations where at least one sibling did not develop HLH, and for patients with biallelic PRF1 missense mutations and an atypical presentation of disease...
December 2015: Pediatric Blood & Cancer
Elisaveta Voynova, Chen-Feng Qi, Bethany Scott, Silvia Bolland
Several mouse models of systemic lupus erythematosus, including FcγRIIB-KO and TLR7tg mice, develop an expansion of an atypical NK cell subset with functional similarity to cells referred as IFN-producing killer DCs or pre-mature NKs in other systems. In this study, we show that atypical NKs purified from spleens of systemic lupus erythematosus-prone mice, and identified as NK1.1(+)CD11c(+)CD122(+)MHC-II(+), induce persistent autoimmune disease in an IFN-I- and CD40L-dependent manner when transferred to wild-type mice...
August 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Olof Berggren, Andrei Alexsson, David L Morris, Karolina Tandre, Gert Weber, Timothy J Vyse, Ann-Christine Syvänen, Lars Rönnblom, Maija-Leena Eloranta
The type I interferon (IFN) system is persistently activated in systemic lupus erythematosus (SLE) and many other systemic autoimmune diseases. Studies have shown an association between SLE and several gene variants within the type I IFN system. We investigated whether single-nucleotide polymorphisms (SNPs) associated with SLE and other autoimmune diseases affect the IFN-α production in healthy individuals. Plasmacytoid dendritic cells (pDCs), B cells and NK cells were isolated from peripheral blood of healthy individuals and stimulated with RNA-containing immune complexes (ICs), herpes simplex virus (HSV) or the oligonucleotide ODN2216...
June 15, 2015: Human Molecular Genetics
J Wild, B J Schmiedel, A Maurer, S Raab, L Prokop, S Stevanović, D Dörfel, P Schneider, H R Salih
Natural killer (NK) cells are cytotoxic lymphocytes that substantially contribute to the therapeutic benefit of antitumor antibodies like Rituximab, a crucial component in the treatment of B-cell malignancies. In chronic lymphocytic leukemia (CLL), the ability of NK cells to lyse the malignant cells and to mediate antibody-dependent cellular cytotoxicity upon Fc receptor stimulation is compromised, but the underlying mechanisms are largely unclear. We report here that NK-cells activation-dependently produce the tumor necrosis factor family member 'B-cell activating factor' (BAFF) in soluble form with no detectable surface expression, also in response to Fc receptor triggering by therapeutic CD20-antibodies...
August 2015: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Contessa E Edgar, Deirdra R Terrell, Sara K Vesely, Jonathan D Wren, Igor M Dozmorov, Timothy B Niewold, Michael Brown, Fang Zhou, Mark Barton Frank, Joan T Merrill, Johanna A Kremer Hovinga, Bernhard Lämmle, Judith A James, James N George, A Darise Farris
Approximately 40% of patients who survive acute episodes of thrombotic thrombocytopenic purpura (TTP) associated with severe acquired ADAMTS13 deficiency experience one or more relapses. Risk factors for relapse other than severe ADAMTS13 deficiency and ADAMTS13 autoantibodies are unknown. ADAMTS13 autoantibodies, TTP episodes following infection or type I interferon treatment and reported ensuing systemic lupus erythematosus in some patients suggest immune dysregulation. This cross-sectional study asked whether autoantibodies against RNA-binding proteins or peripheral blood gene expression profiles measured during remission are associated with history of prior relapse in acquired ADAMTS13-deficient TTP...
2015: PloS One
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