Circular RNAS: novel biomarkers of disease activity in systemic lupus erythematosus?

2019 ◽  
Vol 133 (9) ◽  
pp. 1049-1052 ◽  
Author(s):  
Raquel Cortes ◽  
Maria J. Forner
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Circular Rnas ◽  
Systemic Lupus ◽  
Competitive Endogenous Rnas ◽  
Potential Biomarker ◽  
Inflammatory Processes

Abstract Circular RNAs (circRNAs) are a class of non-coding RNAs that regulate gene expression by acting as competitive endogenous RNAs (ceRNAs) and modulating gene transcription. Several studies support the implication of circRNAs in a variety of human diseases, but research on the role of circRNAs in systemic lupus erythematosus (SLE) is lacking. In a study recently published in Clinical Science (2018), Zhang et al. identified hsa_circ_0012919 as a potential biomarker of disease activity in SLE patients. The authors observed different circRNA expression between SLE patients and healthy controls, an association with clinical variables and with the abnormal DNA methylation present in SLE CD4+ T cells. Finally, Zhang et al. demonstrated that hsa_circ_0012919 acts as a miRNA sponge for miR-125a-3p, regulating the gene expression of targets RANTES and KLF13 that are involved in the physiology and pathophysiology of acute and chronic inflammatory processes. These findings support the role of circRNAs in the pathophysiology of SLE.

scholarly journals Evaluation of the serum β2 Microglobulin level in patients with systemic lupus erythematosus and its correlation with disease activity

BioMedicine ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 16 ◽  
Author(s):  
Miramir Aghdashi ◽  
Simak Salami ◽  
Ahmad Nezhadisalami
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Statistical Tests ◽  
Systemic Lupus ◽  
Β2 Microglobulin ◽  
Reactive Protein ◽  
Significant Difference ◽  
Control Study

Background: Designation of disease activity is serious for the management of systemic lupus erythematosus (SLE). Serum level of β2 microglobulin (β2M) may be associated with illness activity in SLE disease. Since the role of β2M for assessing of illness activity in SLE is not completely clear, the current study aimed to discern evaluation of β2M in patients with SLE and its correlation with sickness activity. Materials and Methods: In this case-control study, 50 patients with SLE disease and 25 healthy individuals were selected in Imam Khomeini Hospital in central of Urmia. Blood samples were collected safely from patients, serum was removed, and β2M measured using an ELISA method. The results for other parameters including C reactive protein, C3, C4, anti dsDNA and erythrocyte sedimentation rate were obtained from patients’ medical record. Data analyzed using appropriate statistical tests including Mann-Whitney U test, Independent f-test, Kruskal-Wallis, and Spearman used for analysis of data. Results: In the current study, a significant difference was seen between two groups in terms of β2M (p < 0.001). Remarkable correlation was seen between the level of β2M with disease activity (p < 0.001). Furthermore, there are significant relevancy between the level of β2M with 24-hour urine protein, ESR, disease activity score, and CRP (p < 0.05). Conclusion: The results revealed that serum amount of β2M in SLE patients is higher compared to healthy ones, which is significantly correlated to score of illness activity, CRP, and ESR in patients with SLE disease. Hence β2M might be an excellent serological marker helping the prediction of sickness activity and inflammation in SLE patients.

scholarly journals Polymorphisms of MFGE8 are associated with susceptibility and clinical manifestations through gene expression modulation in Koreans with systemic lupus erythematosus

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Wook-Young Baek ◽  
Ji-Min Woo ◽  
Hyoun-Ah Kim ◽  
Ju-Yang Jung ◽  
Chang-Hee Suh
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Milk Fat ◽  
Clinical Manifestations ◽  
Αvβ3 Integrin ◽  
Apoptotic Cells ◽  
Systemic Lupus ◽  
Dsdna Antibody

AbstractSystemic lupus erythematosus (SLE) is characterized by impaired clearance of apoptotic cells. Milk fat globule epidermal growth factor 8 (MFGE8) is a protein that connects αvβ3 integrin on phagocytic macrophages with phosphatidylserine on apoptotic cells. We investigated whether genetic variation of the MFGE8 gene and serum MFGE8 concentration are associated with SLE. Single nucleotide polymorphisms (SNPs) were genotyped and serum concentrations were analyzed. The rs2271715 C allele and rs3743388 G allele showed higher frequency in SLE than in healthy subjects (HSs). Three haplotypes were found among 4 SNPs (rs4945, rs1878327, rs2271715, and rs3743388): AACG, CGCG, and CGTC. CGCG haplotype was significantly more common in SLE than in HSs. rs4945 was associated with the erythrocyte sedimentation rate and rs1878327 was associated with alopecia, C-reactive protein, complement 3, anti-dsDNA antibody, and high disease activity. rs2271715 and rs3743388 were associated with renal disease, cumulative glucocorticoid dose, and cyclophosphamide and mycophenolate mofetil use. Serum MFGE8 concentrations were significantly higher in SLE than in HSs. Furthermore, the levels of MFGE8 were significantly higher in SLE than HSs of the rs2271715 CC genotype. In conclusion, MFGE8 genetic polymorphisms are associated not only with susceptibility to SLE but also with disease activity through modulation of gene expression.

Is there any correlation between high sensitive CRP and disease activity in systemic lupus erythematosus?

Lupus ◽  
2011 ◽  
Vol 20 (14) ◽  
pp. 1494-1500 ◽  
Author(s):  
Z Rezaieyazdi ◽  
M Sahebari ◽  
MR Hatef ◽  
B Abbasi ◽  
H Rafatpanah ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Hs Crp

The role of C-reactive protein (CRP) in systemic lupus erythematosus (SLE) as an inflammatory marker is still controversial. Recently, more sensitive methods, such as high sensitive CRP (hs-CRP) have been used to detect micro-inflammation. The role of hs-CRP in lupus flare has not been documented well. We conducted this study to examine the correlation between hs-CRP serum concentrations and disease activity in lupus. Ninety-two SLE patients and 49 healthy controls contributed to our study. Most confounding factors influencing the hs-CRP values were excluded. Disease activity was estimated using the SLE Disease Activity Index (SLEDAI-2K). hs-CRP values were determined using an enzyme-linked immunosorbent assay (ELISA) kit. Serum values of hs-CRP were significantly higher ( p < 0.001, z = 3.29) in patients compared with healthy controls. The cutoff point for hs-CRP between patients and controls was 0.93 mg/L (Youden’s Index = 0.39). There was no correlation between hs-CRP serum levels and disease activity. Furthermore, hs-CRP values did not correlate with any of the laboratory parameters, except for C3 ( p = 0.003, rs = −0.2) and C4 ( p = 0.02, rs = −0.1). Although hs-CRP serum levels were significantly higher in lupus patients compared with healthy controls, it seems that this marker is not a good indicator for disease activity.

scholarly journals Genomic dissection of Systemic Lupus Erythematosus: Distinct Susceptibility, Activity and Severity Signatures

2018 ◽  
Author(s):  
Nikolaos I. Panousis ◽  
George Bertsias ◽  
Halit Ongen ◽  
Irini Gergianaki ◽  
Maria Tektonidou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Whole Blood ◽  
Personalized Therapy ◽  
Flare Activity ◽  
Rna Seq ◽  
Healthy Individuals ◽  
Systemic Lupus

AbstractRecent genetic and genomics approaches have yielded novel insights in the pathogenesis of Systemic Lupus Erythematosus (SLE) but the diagnosis, monitoring and treatment still remain largely empirical1,2. We reasoned that molecular characterization of SLE by whole blood transcriptomics may facilitate early diagnosis and personalized therapy. To this end, we analyzed genotypes and RNA-seq in 142 patients and 58 matched healthy individuals to define the global transcriptional signature of SLE. By controlling for the estimated proportions of circulating immune cell types, we show that the Interferon (IFN) and p53 pathways are robustly expressed. We also report cell-specific, disease-dependent regulation of gene expression and define a core/susceptibility and a flare/activity disease expression signature, with oxidative phosphorylation, ribosome regulation and cell cycle pathways being enriched in lupus flares. Using these data, we define a novel index of disease activity/severity by combining the validated Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)1 with a new variable derived from principal component analysis (PCA) of RNA-seq data. We also delineate unique signatures across disease endo-phenotypes whereby active nephritis exhibits the most extensive changes in transcriptome, including prominent drugable signatures such as granulocyte and plasmablast/plasma cell activation. The substantial differences in gene expression between SLE and healthy individuals enables the classification of disease versus healthy status with median sensitivity and specificity of 83% and 100%, respectively. We explored the genetic regulation of blood transcriptome in SLE and found 3142 cis-expression quantitative trait loci (eQTLs). By integration of SLE genome-wide association study (GWAS) signals and eQTLs from 44 tissues from the Genotype-Tissue Expression (GTEx) consortium, we demonstrate that the genetic causality of SLE arises from multiple tissues with the top causal tissue being the liver, followed by brain basal ganglia, adrenal gland and whole blood. Collectively, our study defines distinct susceptibility and activity/severity signatures in SLE that may facilitate diagnosis, monitoring, and personalized therapy.

scholarly journals Correlation of plasma and urine Wnt5A with the disease activity and cutaneous lesion severity in patients with systemic lupus erythematosus

2021 ◽  
Author(s):  
Shuhong Chi ◽  
Jing Xue ◽  
Xiaodong Chen ◽  
Xiaoming Liu ◽  
Yanhong Ji
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Disease Severity ◽  
Lupus Erythematosus ◽  
Clinical Relevance ◽  
Function Analysis ◽  
Potential Candidate ◽  
Systemic Lupus ◽  
Cutaneous Involvement ◽  
Potential Biomarker

AbstractReliable noninvasive biomarkers are needed to accurately assess disease activity and prognosis in patients with systemic lupus erythematosus (SLE). The purpose of this study was to investigate the clinical relevance of Wnt5A with disease activity and severity with cutaneous involvement in particular in SLE patients; its concentrations in plasma and urine were examined and analyzed. In the cross-sectional study, the clinical relevance of Wnt5A protein was evaluated in both plasma and urine of SLE patients and healthy cohorts using commercial enzyme-linked immunosorbent assays (ELISA). Significantly, more abundances of Wnt5A protein were determined in both of plasmas and urines of SLE patients compared to healthy cohorts (p < 0.0001), which were even higher in active disease (AD) SLE patients relative to low disease activity (LDA) SLE patients (p < 0.0001). Meanwhile, the ROC curve analysis demonstrated that the plasma and urine Wnt5A were potential candidate biomarkers for identifying the disease activity and severity in SLE patients. The discriminant function analysis further revealed that the plasma and urine Wnt5A were separated and distinct for AD SLE patients and healthy controls. In consistence, the disease severity was correlated with the plasma and urine Wnt5A as ascertained by CLASI activity score and the prevalence of serositis in SLE patients. These results suggest that Wnt5A, as a summary measure for different inflammatory processes, could be a potential biomarker for accessing the disease activity, and a noninvasive biomarker for evaluating the disease severity in terms of cutaneous involvement in SLE patients.

scholarly journals Extensive fragmentation and re-organization of gene co-expression patterns underlie the progression of Systemic Lupus Erythematosus

2020 ◽  
Author(s):  
Vasilis F. Ntasis ◽  
Nikolaos I. Panousis ◽  
Maria G. Tektonidou ◽  
Emmanouil T. Dermitzakis ◽  
Dimitrios T. Boumpas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Gene Expression Data ◽  
Lupus Erythematosus ◽  
Genome Organization ◽  
Expression Data ◽  
Systemic Lupus ◽  
Gene Coexpression ◽  
Kidney Involvement

AbstractSystemic Lupus Erythematosus (SLE) is the prototype of autoimmune diseases, characterized by extensive gene expression perturbations in peripheral blood immune cells. Circumstantial evidence suggests that these perturbations may be due to altered epigenetic profiles and chromatin accessibility but the relationship between transcriptional deregulation and genome organization remains largely unstudied. We developed a genomic approach that leverages patterns of gene coexpression from genome-wide transcriptome profiles in order to identify statistically robust Domains of Co-ordinated gene Expression (DCEs). By implementing this method on gene expression data from a large SLE patient cohort, we identify significant disease-associated alterations in gene co-regulation patterns, which also correlate with the SLE activity status. Low disease activity patient genomes are characterized by extensive fragmentation leading to DCEs of smaller size. High disease activity genomes display excessive spatial redistribution of co-expression domains with expanded and newly-appearing (emerged) DCEs. Fragmentation and redistribution of gene coexpression patterns correlate with SLE-implicated biological pathways and clinically relevant endophenotypes such as kidney involvement. Notably, genes lying at the boundaries of split DCEs of low activity genomes are enriched in the interferon and other SLE susceptibility signatures, suggesting the implication of DCE fragmentation at early disease stages. Interrogation of promoter-enhancer interactions from various immune cell subtypes shows that a significant percentage of nested connections are disrupted by a DCE split or depletion in SLE genomes. Collectively, our results underlining an important role for genome organization in shaping gene expression in SLE, could provide valuable insights into disease pathogenesis and the mechanisms underlying disease flares.SignificanceAlthough widespread gene expression changes have been reported in Systemic Lupus Erythematosus (SLE), attempts to link gene deregulation with genome structure have been lacking. Through a computational framework for the segmentation of gene expression data, we reveal extensive fragmentation and reorganization of gene co-regulation domains in SLE, that correlates with disease activity states. Gene co-expression domains pertaining to biological functions implicated in SLE such as the interferon pathway, are being disrupted in patients, while others associated to severe manifestations such as nephritis, emerge in previously uncorrelated regions of the genome. Our results support extensive genome re-organization underlying aberrant gene expression in SLE, which could assist in the early detection of disease flares in patients that are in remission.Graphical Abstract

scholarly journals Downregulated Serum Exosomal miR-451a Expression Correlates With Renal Damage and Its Intercellular Communication Role in Systemic Lupus Erythematosus

2021 ◽  
Vol 12 ◽  
Author(s):  
Lina Tan ◽  
Ming Zhao ◽  
Haijing Wu ◽  
Yuezhong Zhang ◽  
Xiaoliang Tong ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Intercellular Communication ◽  
Lupus Erythematosus ◽  
Renal Damage ◽  
Systemic Lupus ◽  
Immune Imbalance ◽  
Serum Exosomes

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease characterized by continuous inflammation and the production of autoantibodies. Exosomes, acting as a critical tool for communication between cells, are involved in the pathogenesis of SLE, particularly in inflammation and immune imbalance. In this study, we aimed to extract and confirm the pro-inflammatory effect of serum exosomes in SLE. Then, we attempted to find differentially expressed exosomal microRNAs in the serum of healthy subjects and SLE patients via miRNA microarray analysis and validated the target exosomal microRNA, exosomal miR-451a, which expression level decreased in serum of SLE patients by RT-qPCR. Furtherly, we analyzed the correlation between exosomal miR-451a and disease activity, kidney damage and typing, and traditional medicine therapy. Finally, we investigated the intercellular communication role of exosomal miR-451a in SLE by co-culture assay in vitro. Taken together, our study demonstrated that downregulated serum exosomal miR-451a expression correlated with SLE disease activity and renal damage as well as its intercellular communication role in SLE which provided potential therapeutic strategies.

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