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SLE AND T cells

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https://www.readbyqxmd.com/read/29330524/nf-%C3%AE%C2%BAb-inducing-kinase-is-a-therapeutic-target-for-systemic-lupus-erythematosus
#1
Hans D Brightbill, Eric Suto, Nicole Blaquiere, Nandhini Ramamoorthi, Swathi Sujatha-Bhaskar, Emily B Gogol, Georgette M Castanedo, Benjamin T Jackson, Youngsu C Kwon, Susan Haller, Justin Lesch, Karin Bents, Christine Everett, Pawan Bir Kohli, Sandra Linge, Laura Christian, Kathy Barrett, Allan Jaochico, Leonid M Berezhkovskiy, Peter W Fan, Zora Modrusan, Kelli Veliz, Michael J Townsend, Jason DeVoss, Adam R Johnson, Robert Godemann, Wyne P Lee, Cary D Austin, Brent S McKenzie, Jason A Hackney, James J Crawford, Steven T Staben, Moulay H Alaoui Ismaili, Lawren C Wu, Nico Ghilardi
NF-κB-inducing kinase (NIK) mediates non-canonical NF-κB signaling downstream of multiple TNF family members, including BAFF, TWEAK, CD40, and OX40, which are implicated in the pathogenesis of systemic lupus erythematosus (SLE). Here, we show that experimental lupus in NZB/W F1 mice can be treated with a highly selective and potent NIK small molecule inhibitor. Both in vitro as well as in vivo, NIK inhibition recapitulates the pharmacological effects of BAFF blockade, which is clinically efficacious in SLE...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29325308/-opportunistic-infection-in-systemic-lupus-erythematosus-patients-the-disease-spectrum-and-the-characteristics-of-peripheral-lymphocyte-subsets
#2
L Qin, Z F Qiu, J Xie, T R Geng, J L Zhao, L Wan, T S Li
Objective: To investigate the common opportunistic infections and the characteristics of peripheral lymphocyte subsets in patients with systemic lupus erythematosus (SLE). Methods: From December 2013 to December 2016, peripheral lymphocyte subsets were consecutively detected by flow cytometry in treated SLE patients with or without opportunistic infections (OIs) . The lymphocyte subsets in healthy donors were used as normal control group. Results: A total of 145 treated SLE patients were enrolled including 108 with OIs and 37 without OIs...
January 1, 2018: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/29324237/dna-induction-of-mdm2-promotes-proliferation-of-human-renal-mesangial-cells-and-alters-peripheral-b-cells-subsets-in-pediatric-systemic-lupus-erythematosus
#3
Chen-Xing Zhang, Ji Chen, Li Cai, Jing Wu, Jia-Yuan Wang, Lan-Fang Cao, Wei Zhou, Tong-Xin Chen
The study is aimed to investigate the role of MDM2 in the pathogenesis of lupus nephritis (LN) in pediatric SLE (pSLE). We confirmed that MDM2 expression was increased in peripheral blood mononuclear cells (PBMCs) as well as renal specimen of SLE compared with that of controls by western blot and immunofluorescence staining. Percentage of apoptotic and necrotic CD4+T, CD8+T and B cells were detected by flow cytometry respectively and levels of plasma cell free DNA (cfDNA) were quantified in SLE and healthy controls (HC)...
January 8, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29278672/the-initiation-of-autoimmunity-at-epithelial-surfaces-a-focus-on-rheumatoid-arthritis-and-systemic-lupus-erythematosus
#4
Peta Pentony, Laurence Duquenne, Katherine Dutton, Kulveer Mankia, Hanna Gul, Edward Vital, Paul Emery
It is well established that the autoantibodies that characterize both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are present systemically years before patients develop disease. In both these autoimmune rheumatic diseases, evidence is growing that local autoimmune processes occur at epithelial surfaces potentially initiating localized autoimmunity. For RA, these are mucosal surfaces including the oral mucosa, lung, and gut. At the oral mucosa and lung, risk factors such as periodontal disease and smoking may contribute to autoimmunity by driving the local generation of citrullinated autoantigens...
November 2017: Discovery Medicine
https://www.readbyqxmd.com/read/29245286/case-report-for-recurrent-and-new-onset-sle-patients-treated-by-high-dose-glucocorticoid-therapy-characteristics-of-peripheral-tcr-beta-chain-cdr3-repertoires
#5
Jiang Yu, Bin Shi, Long Ma, Chunmei Liu, Suhong Sun, Rui Ma, Yuehong Qiu, Xinsheng Yao
RATIONALE: High-dose glucocorticoid therapy has been widely applied in clinical practice in systemic lupus erythematosus (SLE)patients, but less is known about the changes of T cells, especially the T cell receptor (TCR) repertoires, during the treatment. The aim of this paper is to describe the changes of TCR that recurrent and new-onset SLE patients treated by high-dose glucocorticoid therapy. PATIENT CONCERNS: Drugs of clinical treatment of SLE mainly include glucocorticoid, immunosuppressive agents, nonsteroidal anti-inflammatory drugs and B cell targeted drugs, etc, but the clinical symptoms were in remission and recurrent of onset patients with SLE...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29245125/delayed-type-hypersensitivity-to-metals-in-connective-tissue-diseases-and-fibromyalgia
#6
REVIEW
Geir Bjørklund, Maryam Dadar, Jan Aaseth
Rheumatic diseases include a group of autoimmune disorders with environmental and genetic etiology that are characterized as a subgroup of connective tissue diseases (CTD). Rheumatoid arthritis (RA) often involves the small joints of the hands in a symmetrical fashion that can lead to loss of joint function, and RA, as well as Sjögren's syndrome (SS) and other rheumatic diseases, are often accompanied by sensitivity to metals. Numerous investigations on metal sensitivity were evaluated in this review. A detailed metal exposure history was collected by different evaluation of studies...
December 12, 2017: Environmental Research
https://www.readbyqxmd.com/read/29225917/role-of-p-glycoprotein-on-cd69-cd4-cells-in-the-pathogenesis-of-proliferative-lupus-nephritis-and-non-responsiveness-to-immunosuppressive-therapy
#7
Shizuyo Tsujimura, Tomoko Adachi, Kazuyoshi Saito, Yoshiya Tanaka
Introduction: P-glycoprotein (P-gp) expression on activated lymphocytes in systemic lupus erythematosus (SLE) plays a role in active efflux of intracellular drugs, resulting in drug resistance. The role of P-gp-expressing lymphocytes in the pathogenesis of SLE remains unclear. The aim of this study was to determine the importance of P-gp+CD4+ cells in organ manifestations in refractory SLE. Methods: The proportion of P-gp+CD4+ cells was determined by flow cytometry in peripheral blood of patients with SLE (n=116) and healthy adults (n=10)...
2017: RMD Open
https://www.readbyqxmd.com/read/29224682/calcineurin-inhibitors-in-systemic-lupus-erythematosus
#8
REVIEW
Chi Chiu Mok
The calcineurin inhibitors (CNIs) belong to a group of immunosuppressive agents that block T-cell activation through the suppression of the calcium/calcimodulin-dependent phosphatase calcineurin. Agents such as cyclosporine A (CSA) and tacrolimus (TAC) have long been used in patients with systemic lupus erythematosus (SLE). TAC is preferred to CSA in SLE because of the lower frequency of cosmetic, hypertensive and dyslipidemic adverse effects. Recent randomised controlled trials have demonstrated noninferiority of TAC to mycophenolate mofetil (MMF) or cyclophosphamide (CYC) for induction therapy of lupus nephritis...
June 2017: Best Practice & Research. Clinical Rheumatology
https://www.readbyqxmd.com/read/29224674/drivers-of-the-immunopathogenesis-in-systemic-lupus-erythematosus
#9
REVIEW
Thomas Rose, Thomas Dörner
This review summarises a number of current insights into the pathogenesis of SLE. On the basis of the interaction of environmental factors within a predisposed host, a chronic autoimmune process gains function with a positive feed-forward loop between innate and adaptive immunity. A current focus of SLE pathogenesis is on the enhanced production of certain cytokines, such as type I interferons and BLyS/BAFF, suggesting continuous plasmacytoid dendritic and myeloid cell activity together with disturbances of B lineage cells (increased autoantibodies, including anti-dsDNA and plasmablasts, which correlate with SLE activity and memory B-cell abnormalities)...
June 2017: Best Practice & Research. Clinical Rheumatology
https://www.readbyqxmd.com/read/29219063/an-insight-on-the-pathogenesis-and-treatment-of-systemic-lupus-erythematosus
#10
Murtaza Ali, Chelapram K Firoz, Nasimudeen R Jabir, Mohd Rehan, Mohd Shahnawaz Khan, Shams Tabrez
BACKGROUND AND OBJECTIVE: Systemic lupus erythematosus (SLE) is a diverse autoimmune disorder, evoked in response to self-immune system that leads to immune complex depositions and organ damage. The exact mechanism of SLE pathogenesis is still unclear but certain genetic and environmental factors have been suggested in the literature that could influence its pathogenesis. The modulation in B- and T- cell responses and genetic variations could lead to abnormal lymphocyte functions and the production of antibodies against the indigenous proteins and the immune complex depositions...
December 7, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29214034/identification-of-biomarkers-of-response-to-abatacept-in-patients-with-sle-using-deconvolution-of-whole-blood-transcriptomic-data-from-a-phase-iib-clinical-trial
#11
Somnath Bandyopadhyay, Sean E Connolly, Omar Jabado, June Ye, Sheila Kelly, Michael A Maldonado, Rene Westhovens, Peter Nash, Joan T Merrill, Robert M Townsend
Objective: To characterise patients with active SLE based on pretreatment gene expression-defined peripheral immune cell patterns and identify clusters enriched for potential responders to abatacept treatment. Methods: This post hoc analysis used baseline peripheral whole blood transcriptomic data from patients in a phase IIb trial of intravenous abatacept (~10 mg/kg/month). Cell-specific genes were used with a published deconvolution algorithm to identify immune cell proportions in patient samples, and unsupervised consensus clustering was generated...
2017: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29214033/lupus-related-single-nucleotide-polymorphisms-and-risk-of-diffuse-large-b-cell-lymphoma
#12
Sasha Bernatsky, Héctor A Velásquez García, John J Spinelli, Patrick Gaffney, Karin E Smedby, Rosalind Ramsey-Goldman, Sophia S Wang, Hans-Olov Adami, Demetrius Albanes, Emanuele Angelucci, Stephen M Ansell, Yan W Asmann, Nikolaus Becker, Yolanda Benavente, Sonja I Berndt, Kimberly A Bertrand, Brenda M Birmann, Heiner Boeing, Paolo Boffetta, Paige M Bracci, Paul Brennan, Angela R Brooks-Wilson, James R Cerhan, Stephen J Chanock, Jacqueline Clavel, Lucia Conde, Karen H Cotenbader, David G Cox, Wendy Cozen, Simon Crouch, Anneclaire J De Roos, Silvia de Sanjose, Simonetta Di Lollo, W Ryan Diver, Ahmet Dogan, Lenka Foretova, Hervé Ghesquières, Graham G Giles, Bengt Glimelius, Thomas M Habermann, Corinne Haioun, Patricia Hartge, Henrik Hjalgrim, Theodore R Holford, Elizabeth A Holly, Rebecca D Jackson, Rudolph Kaaks, Eleanor Kane, Rachel S Kelly, Robert J Klein, Peter Kraft, Anne Kricker, Qing Lan, Charles Lawrence, Mark Liebow, Tracy Lightfoot, Brian K Link, Marc Maynadie, James McKay, Mads Melbye, Thierry J Molina, Alain Monnereau, Lindsay M Morton, Alexandra Nieters, Kari E North, Anne J Novak, Kenneth Offit, Mark P Purdue, Marco Rais, Jacques Riby, Eve Roman, Nathaniel Rothman, Gilles Salles, Gianluca Severi, Richard K Severson, Christine F Skibola, Susan L Slager, Alex Smith, Martyn T Smith, Melissa C Southey, Anthony Staines, Lauren R Teras, Carrie A Thompson, Hervé Tilly, Lesley F Tinker, Anne Tjonneland, Jenny Turner, Claire M Vajdic, Roel C H Vermeulen, Joseph Vijai, Paolo Vineis, Jarmo Virtamo, Zhaoming Wang, Stephanie Weinstein, Thomas E Witzig, Andrew Zelenetz, Anne Zeleniuch-Jacquotte, Yawei Zhang, Tongzhang Zheng, Mariagrazia Zucca, Ann E Clarke
Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls...
2017: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29194108/epigenetics-of-inflammatory-arthritis
#13
Deepa Hammaker, Gary S Firestein
PURPOSE OF REVIEW: Aberrant epigenetic changes in DNA methylation, histone marks, and noncoding RNA expression regulate the pathogenesis of many rheumatic diseases. The present article will review the recent advances in the epigenetic profile of inflammatory arthritis and discuss diagnostic biomarkers and potential therapeutic targets. RECENT FINDINGS: Methylation signatures of fibroblast-like synoviocytes not only distinguish rheumatoid arthritis (RA) and osteoarthritis (OA), but also early RAs from late RAs or juvenile idiopathic arthritis...
November 30, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/29192160/a-novel-human-systemic-lupus-erythematosus-model-in-humanised-mice
#14
Merry Gunawan, Zhisheng Her, Min Liu, Sue Yee Tan, Xue Ying Chan, Wilson Wei Sheng Tan, Shubasree Dharmaraaja, Yong Fan, Chee Bing Ong, Eva Loh, Kenneth Tou En Chang, Thiam Chye Tan, Jerry Kok Yen Chan, Qingfeng Chen
Mouse models have contributed to the bulk of knowledge on Systemic Lupus Erythematosus (SLE). Nevertheless, substantial differences exist between human and mouse immune system. We aimed to establish and characterise a SLE model mediated by human immune system. Injection of pristane into immunodeficient mice reconstituted with human immune system (humanised mice) recapitulated key SLE features, including: production of human anti-nuclear autoantibodies, lupus nephritis, and pulmonary serositis. There was a reduction in the number of human lymphocytes in peripheral blood, resembling lymphopenia in SLE patients...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29186654/treatment-with-allogenic-mesenchymal-stromal-cells-in-a-murine-model-of-systemic-lupus-erythematosus
#15
Chiara Tani, Sabrina Vagnani, Linda Carli, Francesca Querci, Anja A Kühl, Simone Spieckermann, Constanze Pamela Cieluch, Simone Pacini, Rita Fazzi, Marta Mosca
Objective: Pre-clinical and uncontrolled studies in patients with systemic lupus erythematosus (SLE) showed that mesenchymal stromal cells (MSCs) have a potential therapeutic role in refractory cases. The optimal therapeutic strategy in these patients remain to be elucidated. Our aim was to test the hypothesis that repeated administrations of 1×106/kg body weight of allogenic MSCs, that is a significantly lower dosage with respect to the fixed 1×106 MSC used in animal models, can be effective in improving the clinical course of a murine SLE model...
November 30, 2017: International Journal of Stem Cells
https://www.readbyqxmd.com/read/29180127/curcumin-a-natural-modulator-of-immune-cells-in-systemic-lupus-erythematosus
#16
REVIEW
Amir Abbas Momtazi-Borojeni, Saeed Mohammadian Haftcheshmeh, Seyed-Alireza Esmaeili, Thomas P Johnston, Elham Abdollahi, Amirhossein Sahebkar
Curcumin is a polyphenol natural product isolated from turmeric, interacting with different cellular and molecular targets and, consequently, showing a wide range of pharmacological effects. Recent preclinical and clinical trials have revealed immunomodulatory properties of curcumin that arise from its effects on immune cells and mediators involved in the immune response, such as various T-lymphocyte subsets and dendritic cells, as well as different inflammatory cytokines. Systemic lupus erythematosus (SLE) is an inflammatory, chronic autoimmune-mediated disease characterized by the presence of autoantibodies, deposition of immune complexes in various organs, recruitment of autoreactive and inflammatory T cells, and excessive levels of plasma proinflammatory cytokines...
November 24, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29175653/igm-antibodies-against-phosphorylcholine-promote-polarization-of-t-regulatory-cells-from-patients-with-atherosclerotic-plaques-systemic-lupus-erythematosus-and-healthy-donors
#17
Jitong Sun, Susanna L Lundström, Bo Zhang, Roman A Zubarev, Johnny Steuer, Peter Gillgren, Mizanur Rahman, Sofia Ajeganova, Anquan Liu, Johan Frostegård
BACKGROUND AND AIMS: IgM antibodies against phosphorylcholine (anti-PC) are negatively associated with atherosclerosis, cardiovascular disease (CVD) and systemic lupus erythematosus (SLE), where the risk of CVD and atherosclerosis is high. We here study the effects of IgM anti-PC immune regulation. METHODS: Mononuclear leukocytes were isolated from peripheral blood (PBMC) obtained from healthy blood donors, six SLE patients with age- and sex-matched controls, and symptom-giving human atherosclerotic plaques...
November 16, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29173182/lupus-nephritis-current-treatment-paradigm-and-unmet-needs
#18
Steven P Menez, Basset El Essawy, Mohamed G Atta
BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by chronic inflammation, which can result in a multitude of systemic or organ-limited manifestations, including the skin, lungs, heart, and kidney. SLE nephritis is present in an average of 38% of patients at the time of diagnosis, and may occur as the initial presentation of disease with progression to end-stage renal disease (ESRD) in roughly 10-20% of patients. METHODS: A review of the current literature was undertaken to investigate the evolution of treatment of SLE nephritis based on randomized trials and robust observational studies...
November 22, 2017: Reviews on Recent Clinical Trials
https://www.readbyqxmd.com/read/29172398/the-evaluation-of-cellular-immune-function-in-elderly-patients-with-systemic-lupus-erythematosus
#19
Kun Men, Yu Chen, Jingwei Zhang, Dianjun Wei
Background/Aims: To evaluate cellular immune function in systemic lupus erythematosus (SLE) patients over 60 years old, the association between antinuclear antibody (ANA) titers and the ratio of CD4+ /CD8+ was analyzed in this study. The distribution of ANAs and extractable nuclear antibodies (ENAs) in a healthy elderly population was also investigated. Methods: Serum ANA titers were assayed by indirect immunofluorescence (IIF) and the CD4+ /CD8+ T-cell ratio was determined by flow cytometry in 76 SLE patients and 30 healthy control individuals...
November 29, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29164585/expression-and-clinical-significance-of-mir-181a-and-mir-203-in-systemic-lupus-erythematosus-patients
#20
H-S Li, Y Ning, S-B Li, P-Y Shao, S-J Chen, Q Ye, X Heng
OBJECTIVE: MiR-181a plays a critical role in modulating T cell and B cell differentiation, as well as immune response. Its abnormal expression probably participates in the pathogenesis of systemic lupus erythematosus (SLE). MiR-203 is involved in regulating Toll-like receptor and inducing immune tolerance. Abnormal expression or function of miR-203 is related to multiple auto-immune diseases but its role in SLE remains unclear. This study, thus, investigated the serum level of miR-181a and miR-203, to analyze their roles in diagnosing and evaluating SLE...
November 2017: European Review for Medical and Pharmacological Sciences
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