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pathogenesis lupus

Lin Xie, Jinhua Xu
OBJECTIVE: T-lymphocyte apoptosis plays a critical role in the pathogenesis of systemic lupus erythematosus (SLE). However, the underlying regulatory mechanisms of apoptosis in SLE remain unclear. The aim of this study was to explore the role of miR-98 in SLE and its underlying mechanisms. METHODS: Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to analyze miR-98 and Fas expression. Luciferase reporter assays were performed to identify miR-98 targets...
June 15, 2018: Journal of Rheumatology
Anne Troldborg, Steffen Thiel, Marten Trendelenburg, Justa Friebus-Kardash, Josephine Nehring, Rudi Steffensen, Søren Werner Karlskov Hansen, Magdalena Janina Laska, Bent Deleuran, Jens Christian Jensenius, Anne Voss, Kristian Stengaard-Pedersen
OBJECTIVE: The pathogenesis of systemic lupus erythematosus (SLE) involves complement activation. Activation of complement through the classical pathway (CP) is well established. However, complement activation through pattern recognition not only happens through the CP, but also through the lectin pathway (LP). We investigated the hypothesis that the LP is activated in SLE and involved in the pathogenesis of the disease. METHODS: Using immunoassays developed in-house, we measured concentrations of LP proteins in a cohort of 372 patients with SLE and 170 controls...
June 15, 2018: Journal of Rheumatology
Tanvi Arkatkar, Holly M Jacobs, Samuel W Du, Quan-Zhen Li, Kelly L Hudkins, Charles E Alpers, David J Rawlings, Shaun W Jackson
B cells are known to promote the pathogenesis of systemic lupus erythematosus (SLE) via the production of pathogenic anti-nuclear antibodies. However, the signals required for autoreactive B cell activation and the immune mechanisms whereby B cells impact lupus nephritis pathology remain poorly understood. The B cell survival cytokine B cell activating factor of the TNF Family (BAFF) has been implicated in the pathogenesis of SLE and lupus nephritis in both animal models and human clinical studies. Although the BAFF receptor has been predicted to be the primary BAFF family receptor responsible for BAFF-driven humoral autoimmunity, in the current study we identify a critical role for signals downstream of Transmembrane Activator and CAML Interactor (TACI) in BAFF-dependent lupus nephritis...
June 12, 2018: Kidney International
Maria G Tektonidou
Kidney damage is a well-recognized complication of the antiphospholipid syndrome (APS), either primary or systemic lupus erythematosus (SLE)-associated APS. Kidney involvement in APS involves a variety of manifestations, such as renal artery thrombosis or stenosis, renal vein thrombosis, allograft loss due to thrombosis after kidney transplantation, and injury to the renal microvasculature, also known as APS nephropathy. Biopsy in patients with APS nephropathy includes acute thrombotic microangiopathy lesions and chronic intrarenal vascular lesions such as interlobular fibrous intimal hyperplasia, arterial and arteriolar recanalizing thrombosis, fibrous arterial occlusion, and focal cortical atrophy...
2018: Frontiers in Immunology
Yongjing Cheng, Xiaozhen Zhao, Yuling Chen, Yuhui Li, Rulin Jia, Lei Zhu, Cibo Huang, Xiaolin Sun, Haiteng Deng, Zhanguo Li
BACKGROUND: Behcet's disease (BD) is a chronic, multisystem-involved vasculitis and its pathogenesis remains elusive. No specific serological markers for BD diagnosis have been established. Identification of novel diagnostic biomarkers will be helpful in timely diagnostic and treatment for Behcet's disease. OBJECTIVE: To screen novel autoantigens or autoantibodies with potential diagnostic value in circulating immune complexes (CICs) from BD patients. METHODS: A proteomic strategy for immune complexome analysis was developed, in which CICs were separated from serum sample of 10 BD patients and 10 healthy controls and then subjected to Orbitrap mass spectrometry for autoantigen profiling...
2018: PloS One
Catherine J Andersen
Cellular cholesterol metabolism, lipid raft formation, and lipoprotein interactions contribute to the regulation of immune-mediated inflammation and response to pathogens. Lipid pathways have been implicated in the pathogenesis of bacterial and viral infections, whereas altered lipid metabolism may contribute to immune dysfunction in autoimmune diseases, such as systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. Interestingly, dietary cholesterol may exert protective or detrimental effects on risk, progression, and treatment of different infectious and autoimmune diseases, although current findings suggest that these effects are variable across populations and different diseases...
June 13, 2018: Nutrients
Yuxuan Zhen, Iris J Lee, Fred D Finkelman, Wen-Hai Shao
Glomerulonephritis (GN) is a typical lesion in autoantibody and immune complex disorders, including SLE. Because the Gas6/Axl pathway has been implicated in the pathogenesis of many types of GN, targeting this pathway might ameliorate GN. Consequently, we have studied the efficacy and mechanism of R428, a potent selective Axl inhibitor, in the prevention of experimental anti-GBM nephritis. Axl upregulation was investigated with Sp1/3 siRNA in the SV40-transformed mesangial cells. For Axl inhibition, a daily dose of R428 (125 mg/kg) or vehicle was administered orally...
June 9, 2018: Journal of Autoimmunity
Valeria Caneparo, Santo Landolfo, Marisa Gariglio, Marco De Andrea
Absent in melanoma 2 (AIM2)-like receptors (ALRs) are a newly characterized class of pathogen recognition receptors (PRRs) involved in cytosolic and nuclear pathogen DNA recognition. In recent years, two ALR family members, the interferon (IFN)-inducible protein 16 (IFI16) and AIM2, have been linked to the pathogenesis of various autoimmune diseases, among which systemic lupus erythematosus (SLE) has recently gained increasing attention. SLE patients are indeed often characterized by constitutively high serum IFN levels and increased expression of IFN-stimulated genes due to an abnormal response to pathogens and/or incorrect self-DNA recognition process...
2018: Frontiers in Immunology
Alexandru Vlagea, Sandra Falagan, Gerardo Gutiérrez-Gutiérrez, Juan Moreno-Rubio, María Merino, Francisco Zambrana, Enrique Casado, María Sereno
Antinuclear antibodies (ANAs) are a spectrum of autoantibodies targeted to various nuclear and cytoplasmic components of the cells. They are very useful as serological markers for different autoimmune disease, like systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), scleroderma, polymyositis, or mixed connective tissue disease. In these years, an increasing attention has been focussed in the relationship between tumours and autoimmunity. Different authors have demonstrated that ANAs are presented, not only in autoimmune diseases, also in serum of patients with different types of cancers...
July 2018: Critical Reviews in Oncology/hematology
Purvi Mande, Bahar Zirak, Wei-Che Ko, Keyon Taravati, Karen L Bride, Tia Y Brodeur, April Deng, Karen Dresser, Zhaozhao Jiang, Rachel Ettinger, Katherine A Fitzgerald, Michael D Rosenblum, John E Harris, Ann Marshak-Rothstein
Toll-like receptors TLR7 and TLR9 are both implicated in the activation of autoreactive B cells and other cell types associated with systemic lupus erythematosus (SLE) pathogenesis. However, Tlr9-/- autoimmune-prone strains paradoxically develop more severe disease. We have now leveraged the negative regulatory role of TLR9 to develop an inducible rapid-onset murine model of systemic autoimmunity that depends on T cell detection of a membrane-bound OVA fusion protein expressed by MHC class II+ cells, expression of TLR7, expression of the type I IFN receptor, and loss of expression of TLR9...
June 11, 2018: Journal of Clinical Investigation
Renaud Felten, Elida Dervovic, François Chasset, Jacques-Eric Gottenberg, Jean Sibilia, Florence Scher, Laurent Arnaud
Currently, Systemic Lupus Erythematosus (SLE) therapies range from antimalarials to glucocorticoids, in addition to immunosupressive agents or biologics such as rituximab or belimumab, when needed. Several unmet needs remain in the treatment SLE and more targeted drugs with improved safety profiles are expected. Based on recent advances in the understanding of the complex pathogenesis of SLE, several targeted treatments are currently assessed in clinical trials. In this study, we performed a systematic review of all targeted therapies under clinical development in SLE in 17 online registries of clinical trials...
June 6, 2018: Autoimmunity Reviews
Katrien Van Raemdonck, Sadiq Umar, Zoltán Szekanecz, Ryan K Zomorrodi, Shiva Shahrara
Obesity can instigate and sustain a systemic low-grade inflammatory environment that can amplify autoimmune disorders and their associated comorbidities. Metabolic changes and inflammatory factors produced by the adipose tissue have been reported to aggravate autoimmunity and predispose the patient to cardiovascular disease (CVD) and metabolic comorbidities. Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are autoimmune arthritic diseases, often linked with altered body mass index (BMI). Severe joint inflammation and bone destruction have a debilitating impact on the patient's life; there is also a staggering risk of cardiovascular morbidity and mortality...
June 6, 2018: Autoimmunity Reviews
Sonya J Wolf, Jonathan Theros, Tammi J Reed, Jianhua Liu, Irina L Grigorova, Giovanny Martínez-Colón, Chaim O Jacob, Jeffrey B Hodgin, J Michelle Kahlenberg
Systemic lupus erythematosus is an autoimmune disease characterized by increased type I IFNs, autoantibodies, and inflammatory-mediated multiorgan damage. TLR7 activation is an important contributor to systemic lupus erythematosus pathogenesis, but the mechanisms by which type I IFNs participate in TLR7-driven pathologic conditions remain uncertain. In this study, we examined the requirement for type I IFNs in TLR7-stimulated lupus nephritis. Lupus-prone NZM2328, INZM (which lack a functional type I IFN receptor), and NZM2328 IL-1β-/- mice were treated at 10 wk of age on the right ear with R848 (TLR7 agonist) or control (DMSO)...
June 8, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Xin Wang, Chengzhong Zhang, Zhouwei Wu, Yue Chen, Weimin Shi
BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic and incurable autoimmune disease involving the dysfunction of lymphocytes. Circular RNAs (circRNAs) are noncoding RNAs (ncRNAs) with a covalently closed loop structure, with abnormal expression in various human diseases may participate in the pathogenesis, while further study is needed in SLE. In this study, we aimed to find the circRNAs abnormally expressed in SLE and explore the function of circRNAs in SLE. METHODS: CircRNA sequencing was used to find the abnormally expressed circRNA and qRT-PCR was used to detect the expression...
June 8, 2018: Arthritis Research & Therapy
Aleksandra Rymarz, Stanisław Niemczyk
BACKGROUND: Catastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening form of antiphospholipid syndrome (APS) involving many organs and leading to their insufficiency. The pathogenesis of CAPS is associated with the presence of antiphospholipid antibodies (aPL). Typical therapy includes anticoagulation, glucocorticoids, therapeutic plasma exchanges and/or intravenous immunoglobulin. Despite this aggressive treatment, the mortality rate of 37% is still high. Novel therapeutic agents are required...
June 8, 2018: BMC Nephrology
Magdalena Dryglewska, Bogdan Kolarz, Maria Majdan
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that results in uncontrolled immune system activation and overproduction of autoantibodies. The pathogenesis of the disease is complex and not fully understood, nevertheless, genetic and environmental factors play an important role. So far, about 30 genes have been identified to be involved in the SLE pathomechanism. However, not all genetically predisposed individuals develop the disease. This phenomenon can be associated with epigenetic changes that occur under the influence of environmental factors...
2018: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
Yan-Mei Mao, Song Wang, Chan-Na Zhao, Qian Wu, Yi-Lin Dan, Shi-Yang Guan, Tian-Tian Lv, Li-Na Liu, Peng Wang, Hai-Feng Pan
BACKGROUND AND AIMS: Matrix metalloproteinase-9 (MMP-9) is closely related to the pathogenesis of autoimmune diseases, especially systemic lupus erythematosus (SLE). However, published works about the circulating MMP-9 levels in SLE are contradictory. A meta-analysis was performed to estimate circulating MMP-9 levels in SLE patients more accurately and explore its related influencing factors. METHODS: The related literatures were systematically searched in PubMed, Embase, and The Cochrane Library database (up to 31 January 2018)...
June 7, 2018: Current Pharmaceutical Design
Junhui He, Mingchong Sun, Sujian Tian
Lupus nephritis (LN) is a multifactorial event that contributes to the long-term mortality of systemic lupus erythematosus (SLE). Activation of NLRP3 inflammasome has been known to play a role in SLE pathogenesis. We evaluated the renal protection effects of procyanidin B2 (PCB2) and the involvement of NLRP3 in a mouse model involving MRL/lpr and MRL/MpJ mice. Kidney injury was evaluated by measuring the renal clinical and pathological features, renal immune complex deposition, and serum anti-double-stranded (anti-dsDNA) Abs...
January 1, 2018: Innate Immunity
Jared S Kahn, Sandhya Chowdary Deverapalli, David M Rosmarin
BACKGROUND: Discoid lupus erythematosus (DLE) and dermatomyositis (DM) are inflammatory autoimmune diseases that manifest primarily in the skin but can be linked to systemic complications. Although there is an in-depth understanding of the clinical presentation of these two diseases, much less is known regarding the pathophysiology. This has limited the effective treatment options for patients. OBJECTIVE: An understanding of the pathogenesis of each disease in greater detail will lead to newer targeted medications with less morbidity...
June 5, 2018: International Journal of Dermatology
Ye He, Amr H Sawalha
PURPOSE OF REVIEW: Rapid introduction of newly developed drugs in the absence of clear understanding of the pathophysiologic mechanisms behind drug-induced lupus erythematosus (DILE) can sometimes make DILE difficult to recognize in clinical practice. The purpose of this review is to summarize drugs most recently reported to be involved in DILE and discuss the current landscape of diverse mechanisms involved. RECENT FINDINGS: A large number of proton pump inhibitor (PPI)-induced subacute cutaneous lupus erythematosus cases have been reported, suggesting a shift over time in the spectrum of drugs implicated in DILE...
June 4, 2018: Current Opinion in Rheumatology
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