scholarly journals The role of baseline BLyS levels and type 1 interferon-inducible gene signature status in determining belimumab response in systemic lupus erythematosus: a post hoc meta-analysis

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Christel Wilkinson ◽  
Robert B. Henderson ◽  
Angela R. Jones-Leone ◽  
Shaun M. Flint ◽  
Mark Lennon ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Meta Analysis ◽  
Gene Signature ◽  
Systemic Lupus ◽  
Type 1 Interferon ◽  
Post Hoc ◽  
Inducible Gene

scholarly journals The peptide symporter SLC15a4 is essential for the development of systemic lupus erythematosus in murine models

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0244439
Author(s):  
Arna Katewa ◽  
Eric Suto ◽  
Jessica Hui ◽  
Jose Heredia ◽  
Jie Liang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Response ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Pharmacological Intervention ◽  
Systemic Lupus ◽  
Autoantibody Production ◽  
Type 1 Interferon ◽  
Cell Functions

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease representing a serious unmet medical need. The disease is associated with the loss of self-tolerance and exaggerated B cell activation, resulting in autoantibody production and the formation of immune complexes that accumulate in the kidney, causing glomerulonephritis. TLR7, an important mediator of the innate immune response, drives the expression of type-1 interferon (IFN), which leads to expression of type-1 IFN induced genes and aggravates lupus pathology. Because the lysosomal peptide symporter slc15a4 is critically required for type-1 interferon production by pDC, and for certain B cell functions in response to TLR7 and TLR9 signals, we considered it as a potential target for pharmacological intervention in SLE. We deleted the slc15a4 gene in C57BL/6, NZB, and NZW mice and found that pristane-challenged slc15a4-/- mice in the C57BL/6 background and lupus prone slc15a4-/- NZB/W F1 mice were both completely protected from lupus like disease. In the NZB/W F1 model, protection persisted even when disease development was accelerated with an adenovirus encoding IFNα, emphasizing a broad role of slc15a4 in disease initiation. Our results establish a non-redundant function of slc15a4 in regulating both innate and adaptive components of the immune response in SLE pathobiology and suggest that it may be an attractive drug target.

scholarly journals Role of Vitamin D in Systemic Lupus Erythematosus

2014 ◽  
Vol 2 (4) ◽  
pp. 662-667 ◽  
Author(s):  
Rada Miskovic ◽  
Aleksandra Plavsic ◽  
Jasna Bolpacic ◽  
Sanvila Raskovic ◽  
Mirjana Bogic
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Vitamin D ◽  
Lupus Erythematosus ◽  
Animal Studies ◽  
Potential Role ◽  
Vitamin D Supplementation ◽  
Vitamin D Status ◽  
Systemic Lupus

Vitamin D is a steroid hormone that in addition to its well known role in the metabolism of calcium and phosphorus exerts immunoregulatory properties. Data from animal studies and from prospective clinical trials on patients with rheumatoid arthritis, multiple sclerosis and type 1 diabetes point to the potential role of vitamin D as important environmental factor in the development of autoimmune diseases. Such role of vitamin D in systemic lupus erythematosus (SLE) has not yet been sufficiently studied. This review shows the sources, metabolism and mechanism of action of vitamin D, its effect on the cells of the immune system, prevalence and causes of vitamin D deficiency in patients with SLE, the link between vitamin D status and disease activity as well as recommendations for vitamin D supplementation.

scholarly journals Association between Toll-Like Receptor 4 Polymorphisms and Systemic Lupus Erythematosus Susceptibility: A Meta-Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Weiping Hu ◽  
Senchao Wu ◽  
Yanlin Zhang ◽  
Keshav Raj Sigdel ◽  
Yong Lin ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Meta Analysis ◽  
Positive Association ◽  
Included Study ◽  
Case Control Studies ◽  
Human Immune System ◽  
Systemic Lupus ◽  
Family Aggregation

Family aggregation was observed among systemic lupus erythematosus (SLE) cases, suggesting the genetic factor may contribute to the susceptibility. Toll-like receptors (TLR) play key role in human immune system; in order to gain better insight on the association between TLR4 polymorphisms and SLE risk, a meta-analysis was conducted. In total 4 case-control studies have been included, involving 503 SLE cases and 636 healthy controls. The association between TLR4 polymorphisms and SLE risk was evaluated by calculating pooled odd ratio (OR) and its 95% confidential interval (CI). TheQ-test andI2statistic were used to estimate the degree of heterogeneity. Publication bias among enrolled studies was examined by using Egger’s test and Begg’s test. Overall, there was no evidence of positive association between SLE risk and D299G and T399I polymorphisms in TLR4. The meta-analysis reported a null association between TLR4 polymorphisms and SLE risk in included study populations, but the role of TLR4 polymorphisms in developing SLE among other populations remains undetermined. Moreover, some laboratory studies still discovered the involvement of TLR4 in SLE process. Therefore, the association between TLR4 polymorphisms and SLE risk requires further investigation both in laboratory and in epidemiological efforts.

scholarly journals Pleiotropy of systemic lupus erythematosus risk alleles and cardiometabolic disorders: A phenome-wide association study and inverse-variance weighted meta-analysis

Lupus ◽  
2021 ◽  
pp. 096120332110149
Author(s):  
Vivian K Kawai ◽  
Mingjian Shi ◽  
Ge Liu ◽  
QiPing Feng ◽  
WeiQi Wei ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Type 1 Diabetes ◽  
Lupus Erythematosus ◽  
Meta Analysis ◽  
Systemic Lupus ◽  
Risk Alleles ◽  
Inverse Variance ◽  
Related Risk ◽  
Cardiometabolic Disorders

Objectives To test the hypothesis that genetic predisposition to systemic lupus erythematosus (SLE) increases the risk of cardiometabolic disorders. Methods Using 41 single nucleotide polymorphisms (SNPs) associated with SLE, we calculated a weighted genetic risk score (wGRS) for SLE. In a large biobank we tested the association between this wGRS and 9 cardiometabolic phenotypes previously associated with SLE: atrial fibrillation, ischemic stroke, coronary artery disease, type 1 and type 2 diabetes, obesity, chronic kidney disease, hypertension, and hypercholesterolemia. Additionally, we performed a phenome-wide association analysis (pheWAS) to discover novel clinical associations with a genetic predisposition to SLE. Findings were replicated in the Electronic Medical Records and Genomics (eMERGE) Network. To further define the association between SLE-related risk alleles and the selected cardiometabolic phenotypes, we performed an inverse variance weighted regression (IVWR) meta-analysis. Results The wGRS for SLE was calculated in 74,759 individuals of European ancestry. Among the pre-selected phenotypes, the wGRS was significantly associated with type 1 diabetes (OR [95%CI] =1.11 [1.06, 1.17], P-value = 1.05x10−5). In the PheWAS, the wGRS was associated with several autoimmune phenotypes, kidney disorders, and skin neoplasm; but only the associations with autoimmune phenotypes were replicated. In the IVWR meta-analysis, SLE-related risk alleles were nominally associated with type 1 diabetes (P = 0.048) but the associations were heterogeneous and did not meet the adjusted significance threshold. Conclusion A weighted GRS for SLE was associated with an increased risk of several autoimmune-related phenotypes including type I diabetes but not with cardiometabolic disorders.

scholarly journals POS0788 CIRCULATING EXOSOMES PROMOTE LUPUS NEPHRITIS IN MRL-LPR MICE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 646.3-647
Author(s):  
X. Sha ◽  
X. Ge ◽  
Y. Jin ◽  
T. Chen ◽  
X. Ni ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Western Blot ◽  
Lupus Erythematosus ◽  
Expression Profiles ◽  
Meta Analysis ◽  
Differentially Expressed ◽  
Systemic Lupus ◽  
Exosomal Mirnas

Background:Systemic Lupus Erythematosus (SLE) is a prototypic autoimmune disease that characterized by the loss of self-tolerance and the production of autoantibodies (autoAbs) [1, 2]. Lupus nephritis (LN), the severe organ-threatening manifestations of SLE, could cause massive damage to patients[3, 4]. Currently, some exosomal microRNAs (miRNAs) are considered as potential biomarkers in SLE. However, the role of exosomal miRNAs in Lupus Nephritis (LN) remains unclear.Objectives:The purpose of this study was to investigate molecular mechanism of plasma exosomal miRNAs in the development of Lupus Nephritis.Methods:Circulating exosomes were isolated from plasma of patients with LN, SLE without LN (NLN). Plasma exosomes were authenticated by Western Blot, Nanosight Tracking Analysis (NTA) and transmission electron microscopy (TEM). Fluorescence microscopy of co-cultured plasma exosomes and podocytes demonstrated that exosomes were uptaken into podocytes. Moreover, cell apoptosis and the inflammation factors was assessed using Western Blot. We analyzed the expression profiles of miRNAs in LN and NLN exosomes and the expression profiles of mRNAs of podocytes stimulated with LN and NLN exosomes with the help of next generation sequencing (NGS).Results:We demonstrate that exosomes derived from LN plasma could be taken by neighboring podocytes and promote the apoptosis of podocytes and the expression of inflammation factors. In addition, the sequencing found that miRNAs were differentially expressed in LN and NLN exosomes and mRNAs were differentially expressed in podocytes stimulated with LN and NLN exosomes.Conclusion:LN plasma exosomes have a potency to stimulate the apoptosis of podocytes and the expression of inflammation factors. Moreover, differentially expressed miRNAs in exosomes play a potential role in the development of LN.References:[1]T. Colasanti, A. Maselli, F. Conti, M. Sanchez, C. Alessandri, C. Barbati, D. Vacirca, A. Tinari, F. Chiarotti, A. Giovannetti, F. Franconi, G. Valesini, W. Malorni, M. Pierdominici, E. Ortona, Autoantibodies to estrogen receptor α interfere with T lymphocyte homeostasis and are associated with disease activity in systemic lupus erythematosus, Arthritis and rheumatism, 64 (2012) 778-787.[2]H.A. Al-Shobaili, A.A. Al Robaee, A.A. Alzolibani, Z. Rasheed, Antibodies against 4-hydroxy-2-nonenal modified epitopes recognized chromatin and its oxidized forms: role of chromatin, oxidized forms of chromatin and 4-hydroxy-2-nonenal modified epitopes in the etiopathogenesis of SLE, Disease markers, 33 (2012) 19-34.[3]A. Kaul, C. Gordon, M.K. Crow, Z. Touma, M.B. Urowitz, R. van Vollenhoven, G. Ruiz-Irastorza, G. Hughes, Systemic lupus erythematosus, Nat Rev Dis Primers, 2 (2016) 16039.[4]M.G. Tektonidou, A. Dasgupta, M.M. Ward, Risk of End-Stage Renal Disease in Patients With Lupus Nephritis, 1971-2015: A Systematic Review and Bayesian Meta-Analysis, Arthritis & rheumatology (Hoboken, N.J.), 68 (2016) 1432-1441.Disclosure of Interests:None declared

Association between alcohol intake and the risk of systemic lupus erythematosus: A systematic review and meta-analysis

Lupus ◽  
2021 ◽  
pp. 096120332199191
Author(s):  
Jinghua Wang ◽  
Jinxiang Liu ◽  
Lu Pan ◽  
Lishuang Guo ◽  
Congcong Liu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Alcohol Intake ◽  
Meta Analysis ◽  
Systemic Lupus ◽  
Heavy Alcohol ◽  
Moderate Alcohol Intake ◽  
Heavy Alcohol Intake

Objectives Previous studies have reported inconsistent results on the relationship between alcohol intake and the risk of systemic lupus erythematosus (SLE). Therefore, we conducted a systematic review and meta-analysis to illustrate the potential role of alcohol intake on the progression of SLE. Methods An electronic search of the PubMed, EmBase, and the Cochrane library databases was conducted from their inception up to March 2020. Observational studies that investigated the role of alcohol intake on the risk of SLE were eligible for inclusion in this study. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated as an effect estimate using the random-effects model. Results Seven case-control studies (n = 3, 251) and three cohort studies (n = 322, 479) were selected for the final meta-analysis. Mild (OR: 0.85; 95% CI: 0.53–1.38; p = 0.515) or heavy (OR: 0.63; 95% CI: 0.37–1.09; p = 0.102) alcohol intake were not associated with the risk of SLE, while moderate alcohol intake could protect against the risk of SLE (OR: 0.71; 95% CI: 0.55–0.93; p = 0.012). Sensitivity analysis suggested that heavy alcohol intake was associated with a reduced risk of SLE (OR: 0.47; 95% CI: 0.32–0.67; p < 0.001). Conclusions This study found that moderate alcohol intake could protect against the risk of SLE, while mild or heavy alcohol intake did not significantly affect the risk of SLE.

Sign in / Sign up

Export Citation Format

Share Document