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https://www.readbyqxmd.com/read/28691866/safety-and-pharmacodynamics-of-venetoclax-abt-199-in-a-randomized-single-and-multiple-ascending-dose-study-in-women-with-systemic-lupus-erythematosus
#1
P Lu, R Fleischmann, C Curtis, S Ignatenko, S H Clarke, M Desai, S L Wong, K M Grebe, K Black, J Zeng, J Stolzenbach, J K Medema
Objective The anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) may contribute to the pathogenesis of systemic lupus erythematosus. The safety, tolerability, and pharmacodynamics of the selective Bcl-2 inhibitor venetoclax (ABT-199) were assessed in women with systemic lupus erythematosus. Methods A phase 1, double-blind, randomized, placebo controlled study evaluated single ascending doses (10, 30, 90, 180, 300, and 500 mg) and multiple ascending doses (2 cycles; 30, 60, 120, 240, 400, and 600 mg for 1 week, and then 3 weeks off per cycle) of orally administered venetoclax...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28593610/brief-report-decreased-expression-of-cd244-slamf4-on-monocytes-and-platelets-in-patients-with-systemic-lupus-erythematosus
#2
Anselm Mak, Susannah I Thornhill, Hui Yin Lee, Bernett Lee, Michael Poidinger, John E Connolly, Anna-Marie Fairhurst
The signalling lymphocyte activation molecule (SLAM) family receptors play important roles in modulating immune responses. Previous studies in murine models and patients have suggested an association of the SLAM family (SLAMF) members with the development of autoimmunity, particularly systemic lupus erythematosus (SLE). Since previous investigations on CD244 expression have focussed on NK and T cells, the aim of this study was to evaluate the surface expression of major SLAMF members across monocytes and polymorphonuclear cells in an Asian SLE cohort and explore their potential associations with SLE-related disease activity and autoantibodies...
June 8, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28555437/autoimmunity-in-2016
#3
REVIEW
Carlo Selmi
The number of peer-reviewed articles published during the 2016 solar year and retrieved using the "autoimmunity" key word remained stable while gaining a minimal edge among the immunology articles. Nonetheless, the quality of the publications has been rising significantly and, importantly, acquisitions have become available through scientific journals dedicated to immunology or autoimmunity. Major discoveries have been made in the fields of systemic lupus erythematosus, rheumatoid arthritis, autoimmunity of the central nervous system, vasculitis, and seronegative spondyloarthrithritides...
August 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28545118/atopy-in-children-with-juvenile-systemic-lupus-erythematosus-is-associated-with-severe-disease
#4
Ruru Guo, Yanqing Zhou, Liangjing Lu, Lanfang Cao, Junjia Cao
The influence of co-existing atopy on the prognosis of juvenile systemic lupus erythematosus (JSLE) was assessed in this study. Patients diagnosed with JSLE between October 2005 and April 2016 were enrolled in a prospective study and followed up for 2 years. Management of patients was evaluated using the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) score and laboratory variables. Eighty JSLE patients were enrolled at diagnosis and divided into those with (n = 35) and without (n = 45) atopy...
2017: PloS One
https://www.readbyqxmd.com/read/28534426/the-immunological-personality-of-close-relatives-of-sle-patients
#5
M R Salaman, D A Isenberg
Immunological abnormalities seen in relatives of patients with autoimmune disorders can be useful in understanding the pathogenesis of the disease since, unlike in patients, they cannot result from the disease process or drug treatment. In this article we present a brief overview of our studies of the basic immunological status of close relatives of SLE patients. We looked at blood levels of IgG, IgM and antibodies to double-stranded DNA, as well as at NK cell numbers and cytotoxic activity and the levels of NKT, B and T cells...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28523761/unraveling-the-expression-of-microrna-27a-nkg2d-in-peripheral-blood-mononuclear-cells-and-natural-killer-cells-of-pediatric-systemic-lupus-erythematosus-patients
#6
Shady K Sourour, Heba R Aboelenein, Noha M Elemam, Amira K Abdelhamid, Samia Salah, Ahmed I Abdelaziz
BACKGROUND AND AIM: The activity of natural killer (NK) cells is known to be decreased in systemic lupus erythematosus (SLE) patients. Nevertheless, the exact contribution of NK cells in the pathogenesis of SLE is still inconclusive. MicroRNAs (miRNAs), are small noncoding RNA molecules that play a fundamental role in regulating NK cell function. The objective of this study was to investigate the expression of miRNAs that might potentially target an essential activating receptor, NKG2D in peripheral blood mononuclear cells (PBMCs) and NK cells of SLE patients...
May 19, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28474288/could-lymphocyte-profiling-be-useful-to-diagnose-systemic-autoimmune-diseases
#7
REVIEW
Guillermo Carvajal Alegria, Pierre Gazeau, Sophie Hillion, Claire I Daïen, Divi Y K Cornec
Considering the implications of B, T, and natural killer (NK) cells in the pathophysiology of systemic autoimmune diseases, the assessment of their distribution in the blood could be helpful for physicians in the complex process of determining a precise diagnosis. In primary Sjögren's syndrome, transitional and active naive B cells are increased and memory B cells are decreased compared to healthy controls and other systemic diseases. However, their utility to improve the accuracy of classification criteria has not been proven...
May 4, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28407142/obinutuzumab-induces-superior-b-cell-cytotoxicity-to-rituximab-in-rheumatoid-arthritis-and-systemic-lupus-erythematosus-patient-samples
#8
Venkat Reddy, Christian Klein, David A Isenberg, Martin J Glennie, Geraldine Cambridge, Mark S Cragg, Maria J Leandro
Objective.: A proportion of RA and SLE patients treated with standard doses of rituximab (RTX) display inefficient B cell deletion and poor clinical responses that can be augmented by delivering higher doses, indicating that standard-dose RTX is a sub-optimal therapy in these patients. This study aimed to investigate whether better responses could be achieved with mechanistically different anti-CD20 mAbs. Methods.: We compared RTX with obinutuzumab (OBZ), a new-generation, glycoengineered type II anti-CD20 mAb, in a series of in vitro assays measuring B cell cytotoxicity in RA and SLE patient samples...
April 11, 2017: Rheumatology
https://www.readbyqxmd.com/read/28237724/the-common-autoimmunity-predisposing-620arg%C3%A2-%C3%A2-trp-variant-of-ptpn22-modulates-macrophage-function-and-morphology
#9
Meihang Li, Hugues Beauchemin, Natalija Popovic, Alan Peterson, Eva d'Hennezel, Ciriaco A Piccirillo, Chao Sun, Constantin Polychronakos
The C1858T single nucleotide polymorphism (SNP) in PTPN22 (protein tyrosine phosphatase nonreceptor 22) leads to the 620 Arg to Trp polymorphism in its encoded human protein LYP. This allelic variant is associated with multiple autoimmune diseases, including type 1 diabetes (T1D), Crohn's disease, rheumatoid arthritis and systemic lupus erythematosus. However, the underlying mechanisms are poorly understood. To study how this polymorphism influences the immune system, we generated a mouse strain with a knock-in of the Trp allele, imitating the human disease-associated variant...
February 22, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28111707/hpv-and-systemic-lupus-erythematosus-a-mosaic-of-potential-crossreactions
#10
Yahel Segal, Shani Dahan, Michele Calabrò, Darja Kanduc, Yehuda Shoenfeld
Etiology, pathogenesis, and immunology of systemic lupus erythematosus (SLE) form a complex, still undeciphered picture that recently has been further made complicated by a new factor of morbidity: human papillomaviruses (HPVs). Indeed, a prevalence of HPV infections has been reported among SLE patients. Searching for molecular mechanisms that might underlie and explain the relationship between HPV infection and SLE, we explored the hypothesis that immune responses following HPV infection may crossreact with proteins that, when altered, associate with SLE...
April 2017: Immunologic Research
https://www.readbyqxmd.com/read/28076903/signaling-lymphocytic-activation-molecule-family-member-7-engagement-restores-defective-effector-cd8-t-cell-function-in-systemic-lupus-erythematosus
#11
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 systemic lupus erythematosus (SLE) and is associated with a compromised ability to fight infections. Signaling lymphocytic activation molecule family member 7 (SLAMF7) engagement has been shown to enhance natural killer cell degranulation. This study was undertaken to characterize the expression and function of SLAMF7 on CD8+ T cell subsets isolated from the peripheral blood of SLE patients and healthy subjects. METHODS: CD8+ T cell subset distribution, SLAMF7 expression, and expression of cytolytic enzymes (perforin, granzyme A [GzmA], and GzmB) on cells isolated from SLE patients and healthy controls were analyzed by flow cytometry...
May 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27847409/effect-of-interleukin-15-on-cd11b-cd54-and-cd62l-expression-on-natural-killer-cell-and-natural-killer-t-like-cells-in-systemic-lupus-erythematosus
#12
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
https://www.readbyqxmd.com/read/27733745/unusual-association-of-hemophagocytic-lymphohistiocytosis-in-systemic-lupus-erythematosus-cases-reported-at-tertiary-care-center
#13
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
https://www.readbyqxmd.com/read/27576056/novel-molecular-signatures-in-mononuclear-cell-populations-from-patients-with-systemic-lupus-erythematosus
#14
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
https://www.readbyqxmd.com/read/27444334/coexistence-of-sle-tuberous-sclerosis-and-aggressive-natural-killer-cell-leukaemia-coincidence-or-correlated
#15
LETTER
S Psarelis, E Nikiphorou
No abstract text is available yet for this article.
January 2017: Lupus
https://www.readbyqxmd.com/read/27424138/evaluation-of-pbmc-distribution-and-tlr9-expression-in-patients-with-systemic-lupus-erythematosus
#16
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
https://www.readbyqxmd.com/read/27118513/the-complement-receptor-3-cd11b-cd18-agonist-leukadherin-1-suppresses-human-innate-inflammatory-signalling
#17
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
https://www.readbyqxmd.com/read/26989167/analysis-of-killer-cell-immunoglobulin-like-receptors-and-their-human-leukocyte-antigen-ligands-gene-polymorphisms-in-iranian-patients-with-systemic-lupus-erythematosus
#18
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
https://www.readbyqxmd.com/read/26964093/il-10-production-is-critical-for-sustaining-the-expansion-of-cd5-b-and-nkt-cells-and-restraining-autoantibody-production-in-congenic-lupus-prone-mice
#19
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
https://www.readbyqxmd.com/read/26946293/coexistence-of-systemic-lupus-erythematosus-tuberous-sclerosis-and-aggressive-natural-killer-cell-leukaemia-coincidence-or-correlated
#20
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
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