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b cells AND SLE AND T cells

Gabriela Recalde, Tamara Moreno-Sosa, Florencia Yudica, Cristian A Quintero, Belén Sanchez, Graciela A Jahn, Alexis M Kalergis, Juan Pablo Mackern-Oberti
In this review we discuss how sex steroids and prolactin affect regulation and responsiveness of B and T cells. Sex hormones exert profound effects on several physiological processes of non- reproductive tissues. In the immune system, several studies with experimental models for SLE have shown a noticeable pro-inflammatory role for ERα, contributing to disease development reflected in proteinuria and renal pathology. On the other hand, ERβ appears to have an anti- inflammatory and immunosuppressive effect...
March 8, 2018: Autoimmunity Reviews
Laurence E Cheng, Zahir Amoura, Benjamin Cheah, Falk Hiepe, Barbara A Sullivan, Lei Zhou, Gregory E Arnold, Wayne H Tsuji, Joan T Merrill, James B Chung
OBJECTIVE: Evaluate the safety and potential efficacy of AMG 557, a fully human antibody directed against the inducible T-cell costimulator ligand (ICOSL), in patients with systemic lupus erythematosus (SLE) with arthritis. METHODS: In this phase 1b, randomized, double-blind, placebo-controlled study, patients received AMG 557 210 mg (n=10) or placebo (n=10) weekly for 3 weeks, then every other week for 10 additional doses. Corticosteroids were tapered to ≤7...
March 7, 2018: Arthritis & Rheumatology
Peng Zhang, Qianjin Lu
Immunological tolerance loss is fundamental to the development of autoimmunity; however, the underlying mechanisms remain elusive. Immune tolerance consists of central and peripheral tolerance. Central tolerance, which occurs in the thymus for T cells and bone marrow for B cells, is the primary way that the immune system discriminates self from non-self. Peripheral tolerance, which occurs in tissues and lymph nodes after lymphocyte maturation, controls self-reactive immune cells and prevents over-reactive immune responses to various environment factors...
March 5, 2018: Cellular & Molecular Immunology
R J Zhang, X Zhang, J Chen, M Shao, Y Yang, B Balaubramaniam, X L Sun, J L Ambrus, J He, Z G Li
Objective Serum soluble CD25 (sCD25) could be used as a biomarker for disease activity in conditions associated with T-cell activation including various autoimmune diseases. This study aimed to explore the role of sCD25 as an indicator of disease activity and organ involvement in patients with systemic lupus erythematosus (SLE). Methods Serum samples were collected from 107 SLE patients and 92 age-matched healthy controls (HCs). All patients were followed up for 24 weeks, and sCD25 was measured by enzyme-linked immunosorbent assay...
January 1, 2018: Lupus
Sonia Zeggar, Katsue S Watanabe, Sanae Teshigawara, Sumie Hiramatsu, Takayuki Katsuyama, Eri Katsuyama, Haruki Watanabe, Yoshinori Matsumoto, Tomoko Kawabata, Ken-Ei Sada, Toshiro Niki, Mitsuomi Hirashima, Jun Wada
OBJECTIVE: In systemic lupus erythematosus (SLE), an autoimmune disease associated with multiple organ involvements, lupus nephritis determines prognosis and arthritis impairs quality of life of patients. Galectin-9 (Gal-9, Lgals9) is a β-galactoside binding lectin and the attempts for its clinical application have been made in autoimmune diseases, since recombinant Gal-9 as a ligand for Tim-3 induces apoptosis in activated CD4+ Tim-3+ Th1 cell. We investigated wethere the deficiency of Lgals9 is beneficial or deleterious in lupus mice models...
February 26, 2018: Arthritis & Rheumatology
K E Cervantes-Luevano, N Caronni, M C Castiello, E Fontana, G Piperno, A Naseem, P Uva, M Bosticardo, G E Marcovecchio, L D Notarangelo, M P Cicalese, A Aiuti, A Villa, F Benvenuti
BACKGROUND: Wiskott-Aldrich syndrome (WAS) is a rare primary immunodeficiency caused by mutations in WASp, a key regulator of cytoskeletal dynamics in hematopoietic cells. A high proportion of patients develop autoimmunity due to a breakdown in T and B cell tolerance. Moreover, excessive production of type-I interferon by plasmacytoid DCs contribute to autoimmune signs, however, the factors that triggers excessive innate activation have not been defined. OBJECTIVE: Neutrophils extracellular traps (NETs) emerged as major initiating factors in diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA)...
February 12, 2018: Journal of Allergy and Clinical Immunology
Wei Liang, Shanshan Mao, Shijie Sun, Ming Li, Zhi Li, Rui Yu, Tonghui Ma, Jianguo Gu, Jianing Zhang, Naoyuki Taniguchi, Wenzhe Li
CD4+ T cell activation promotes the pathogenic process of systemic lupus erythematosus (SLE). T cell receptor (TCR) complex are highly core fucosylated glycoproteins, which play important roles in T cell activation. In this study, we found that the core fucosylation of CD4+ T cells was significantly increased in SLE patients. Loss of core fucosyltransferase (Fut8), the sole enzyme for catalyzing the core fucosylation of N-glycan, significantly reduced CD4+ T cell activation and ameliorated the experimental autoimmune encephalomyelitis-induced syndrome in Fut8-/- mice...
2018: Frontiers in Immunology
Chen Liu, Dongwei Wang, Ying Song, Songsong Lu, Jingzhong Zhao, Hui Wang
As one specialized subset of regulatory T cells (Tregs), follicular regulatory T cells (TFR) could suppress follicular helper T cells (TFH) and B cells in germinal centers to maintain immune homeostasis. The unbalance of TFR and TFH cells could result in abnormal germinal center responses and contribute to pathogenesis of autoimmune diseases. However, the role of TFR cells in systemic lupus erythematosus (SLE) remains unclear. This study revealed a significant increase of CD4+CXCR5+FOXP3+ TFR cells in peripheral blood of SLE patients compared with healthy controls...
January 30, 2018: International Immunopharmacology
L F da Rosa Franchi Santos, N P Stadtlober, L G Costa Dall'Aqua, B M Scavuzzi, P M Guimarães, T Flauzino, M A Batisti Lozovoy, T V Mayumi Iriyoda, E M Vissoci Reiche, I Dichi, M Maes, A Colado Simão
Background This study was performed to assess adhesion molecules in systemic lupus erythematosus (SLE). Methods This case-control study examined 126 SLE patients and 48 healthy individuals. Blood levels of six adhesion molecules, cortisol, nuclear autoantibody (ANA) and anti-double stranded DNA (anti-dsDNA) titers were measured, while disease activity was assessed using the SLE Disease Activity Index (SLEDAI) score. Results Platelet endothelial cell adhesion molecule 1 (PECAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, P-selectin, and plasminogen activator inhibitor type-1 (PAI-1) were significantly higher in SLE patients than in controls...
January 1, 2018: Lupus
Hannah A Blair, Sean T Duggan
Belimumab (Benlysta®) is a human immunoglobulin G1λ monoclonal antibody that inhibits the binding of soluble B lymphocyte stimulator to B cells. It is the only biological agent currently approved for the treatment of non-renal systemic lupus erythematosus (SLE). Belimumab is approved in the EU, the USA and other countries as add-on therapy in adult patients with active, autoantibody-positive SLE despite standard therapy. In phase III trials, treatment with IV or SC belimumab plus standard therapy was effective in terms of reducing overall disease activity and reducing the incidence and severity of flares, without worsening of patients' overall condition or the development of significant disease activity in new organ systems...
February 2, 2018: Drugs
J Waldron, W Raymond, G Ostli-Eilertsen, J Nossent
Background Insulin growth factor-1 (IGF1) activates cell proliferation pathways and inhibits apoptosis. IGF1 is involved in tumour growth and required for T-cell independent activation of B cells. Activated B cells and autoantibody production are a hallmark of systemic lupus erythematosus (SLE). To investigate the possible role of IGF1 in SLE, we studied IGF1 across clinical characteristics, immunological biomarkers, disease activity and organ damage in SLE patients. Method In a cross-sectional study, we collected clinical characteristics, medication, disease activity (SLEDAI-2K) and organ damage (SDI) for 94 SLE patients...
January 1, 2018: Lupus
Erin B Taylor, Michelle T Barati, David W Powell, Hannah R Turbeville, Michael J Ryan
Numerous studies show a direct relation between circulating autoantibodies, characteristic of systemic autoimmune disorders, and primary hypertension in humans. Whether these autoantibodies mechanistically contribute to the development of hypertension remains unclear. Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by aberrant immunoglobulin production, notably pathogenic autoantibodies, and is associated with prevalent hypertension, renal injury, and cardiovascular disease...
January 29, 2018: Hypertension
Mélanie Souyris, Claire Cenac, Pascal Azar, Danièle Daviaud, Astrid Canivet, Solange Grunenwald, Catherine Pienkowski, Julie Chaumeil, José E Mejía, Jean-Charles Guéry
Toll-like receptor 7 (TLR7) is critical to the induction of antiviral immunity, but TLR7 dosage is also a key pathogenic factor in systemic lupus erythematosus (SLE), an autoimmune disease with strong female bias. SLE prevalence is also elevated in individuals with Klinefelter syndrome, who carry one or more supernumerary X chromosomes, suggesting that the X chromosome complement contributes to SLE susceptibility. TLR7 is encoded by an X chromosome locus, and we examined here whether the TLR7 gene evades silencing by X chromosome inactivation in immune cells from women and Klinefelter syndrome males...
January 26, 2018: Science Immunology
Samantha A Chalmers, Jing Wen, Jessica Doerner, Ariel Stock, Carla M Cuda, Hadijat M Makinde, Harris Perlman, Todd Bosanac, Deborah Webb, Gerald Nabozny, Jay S Fine, Elliott Klein, Meera Ramanujam, Chaim Putterman
BACKGROUND: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that affects different end organs, including skin and brain. We and others have previously shown the importance of macrophages in the pathogenesis of cutaneous and neuropsychiatric lupus. Additionally, autoantibodies produced by autoreactive B cells are thought to play a role in both the skin and central nervous system pathologies associated with SLE. METHODS: We used a novel inhibitor of Bruton's tyrosine kinase (BTK), BI-BTK-1, to target both macrophage and B cell function in the MRL-lpr/lpr murine model of SLE, and examined the effect of treatment on skin and brain disease...
January 25, 2018: Arthritis Research & Therapy
Constance J Ulff-Møller, Fazila Asmar, Yi Liu, Anders J Svendsen, Florence Busato, Kirsten Grønbaek, Jörg Tost, Søren Jacobsen
OBJECTIVE: Systemic lupus erythematosus (SLE) has limited monozygotic (MZ) twin concordance, implying a role for other pathogenic factors than genetic variation, such as epigenetic changes. Using the disease discordant twin model, we investigated genome-wide DNA methylation changes in sorted CD4+ T-cells, monocytes, granulocytes and B-cells in twin pairs with at least one SLE-affected twin. METHODS: Peripheral blood from 15 SLE twin pairs (six MZ, nine dizygotic (DZ)) was processed using gradient density centrifugation for the granulocyte fraction...
January 23, 2018: Arthritis & Rheumatology
Lunhua Liu, Windy Rose Allman, Adam Steven Coleman, Kazuyo Takeda, Tsai-Lien Lin, Mustafa Akkoyunlu
Anti-B cell activating factor belonging to TNF-family (BAFF) antibody therapy is indicated for the treatment of patients with active systemic lupus erythematosus (SLE). We hypothesized that the BAFF receptor, transmembrane activator and calcium-modulator and cyclophilin interactor (TACI) may be responsible for the generation of antibody secreting plasma cells in SLE. To test this hypothesis, we generated TACI deficient MRL-Fas/Lpr (LPR-TACI-/-) mouse. TACI deficiency resulted in improved survival of MRL-Fas/Lpr mice and delayed production of anti-dsDNA and anti-SAM/RNP antibodies...
January 22, 2018: Scientific Reports
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
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
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)
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
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