scholarly journals IFN-γ Mediates the Development of Systemic Lupus Erythematosus

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Wenping Liu ◽  
Mengdi Li ◽  
Ziye Wang ◽  
Jibo Wang
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Antigen Processing ◽  
Fiber Formation ◽  
The Body ◽  
Interferon Α ◽  
Systemic Lupus ◽  
Bioinformatics Analyses ◽  
Ifn Γ

Objective. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect all organs in the body. It is characterized by overexpression of antibodies against autoantigen. Although previous bioinformatics analyses have identified several genetic factors underlying SLE, they did not discriminate between naive and individuals exposed to anti-SLE drugs. Here, we evaluated specific genes and pathways in active and recently diagnosed SLE population. Methods. GSE46907 matrix downloaded from Gene Expression Omnibus (GEO) was analyzed using R, Metascape, STRING, and Cytoscape to identify differentially expressed genes (DEGs), enrichment pathways, protein-protein interaction (PPI), and hub genes between naive SLE individuals and healthy controls. Results. A total of 134 DEGs were identified, in which 29 were downregulated, whereas 105 were upregulated in active and newly diagnosed SLE cases. GO term analysis revealed that transcriptional induction of the DEGs was particularly enhanced in response to secretion of interferon-γ and interferon-α and regulation of cytokine production innate immune responses among others. KEGG pathway analysis showed that the expression of DEGs was particularly enhanced in interferon signaling, IFN antiviral responses by activated genes, class I major histocompatibility complex (MHC-I) mediated antigen processing and presentation, and amyloid fiber formation. STAT1, IRF7, MX1, OASL, ISG15, IFIT3, IFIH1, IFIT1, OAS2, and GBP1 were the top 10 DEGs. Conclusions. Our findings suggest that interferon-related gene expression and pathways are common features for SLE pathogenesis, and IFN-γ and IFN-γ-inducible GBP1 gene in naive SLE were emphasized. Together, the identified genes and cellular pathways have expanded our understanding on the mechanism underlying development of SLE. They have also opened a new frontier on potential biomarkers for diagnosis, biotherapy, and prognosis for SLE.

Gene expression of cytokines (TNF-α, IFN-γ), serum profiles of IL-17 and IL-23 in paediatric systemic lupus erythematosus

Lupus ◽  
2012 ◽  
Vol 21 (10) ◽  
pp. 1105-1112 ◽  
Author(s):  
A Rana ◽  
RW Minz ◽  
R Aggarwal ◽  
S Anand ◽  
N Pasricha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Tnf Α ◽  
Ifn Γ

Type I interferon gene signature test–low and –high patients with systemic lupus erythematosus have distinct gene expression signatures

Lupus ◽  
2019 ◽  
Vol 28 (13) ◽  
pp. 1524-1533 ◽  
Author(s):  
PZ Brohawn ◽  
K Streicher ◽  
B W Higgs ◽  
C Morehouse ◽  
H Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Type I Interferon ◽  
Gene Signature ◽  
Type I ◽  
Type I Ifn ◽  
Systemic Lupus ◽  
Blood Samples ◽  
Ifn Γ

Objectives Type I interferon (IFN) is implicated in systemic lupus erythematosus (SLE) pathogenesis. We aimed to identify type I IFN signaling-dependent and -independent molecular pathways in a large population of patients with SLE. Methods Baseline blood samples from adult patients with moderate to severe SLE from two Phase IIb studies (NCT01438489, n = 265; NCT01283139, n = 416) were profiled using whole transcriptome array analyses. Type I IFN gene signature (IFNGS) test status (high or low) was determined using a validated qualitative polymerase chain reaction–based test. IFN-type-specific signatures were developed by stimulating healthy blood with IFN-β, IFN-γ, IFN-λ, IFN-ω, or pooled IFN-α. These, and multiple literature-derived cell type and cytokine pathway signatures, were evaluated in individual and pooled study populations. A Fisher’s exact test was used for associations, adjusted for false discovery rate. Results Whole blood samples from IFNGS test–high patients were enriched versus IFNGS test–low patients for CD40L signaling ( Q < 0.001), CXC cytokine ( Q < 0.001), TLR8-mediated monocyte activation ( Q < 0.001), IgG ( Q < 0.001), major histocompatibility complex class I ( Q < 0.001), and plasma cell ( Q < 0.001) gene expression signatures. IFNGS test–low patients had significant enrichment of eosinophil ( Q < 0.001), IFN-γ-specific ( Q = 0.005), and T-cell or B-cell ( Q < 0.001) signatures. Similar enrichment profiles were demonstrated in patients with primary Sjögren’s syndrome, systemic sclerosis, and dermatomyositis. Conclusions IFNGS test–high patients overexpressed many gene signatures associated with SLE pathogenesis compared with IFNGS test–low patients, reflecting broad immune activation. These results provide new insights into the molecular heterogeneity underlying SLE pathogenesis, highlighting shared mechanisms beyond type I IFN, across several autoimmune diseases. Trial registration Clinicaltrials.gov: NCT01438489 and NCT01283139.

Lack of association between the interferon-α signature and longitudinal changes in disease activity in systemic lupus erythematosus

2008 ◽  
Vol 68 (9) ◽  
pp. 1440-1446 ◽  
Author(s):  
C Landolt-Marticorena ◽  
G Bonventi ◽  
A Lubovich ◽  
C Ferguson ◽  
T Unnithan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Rna Binding ◽  
High Disease Activity ◽  
Poor Correlation ◽  
Interferon Α ◽  
Systemic Lupus ◽  
Dsdna Antibody

Objective:To study the longitudinal expression of interferon (IFN)-inducible genes in systemic lupus erythematosus (SLE) and determine their suitability as disease biomarkers.Methods:RNA was isolated from the peripheral blood of 94 patients with SLE and 11 controls and reverse transcribed into cDNA. The expression levels of five IFN-responsive genes (LY6E, OAS1, IFIT1, ISG15 and MX1) were determined by quantitative PCR, normalised to GAPDH and summed to generate a global IFN score. Patients were followed longitudinally for a period of 3–12 months, and the association between disease activity, as measured by the SLE disease activity index (SLEDAI-2K), and other clinical and laboratory variables was examined.Results:The expression of all five IFN-responsive genes was significantly higher in patients with SLE than in controls. The expression of LY6E, OAS1, IFIT1 and the global IFN score was associated with high disease activity. The global IFN score was also associated with active renal disease, a decreased C3, and the presence of anti-dsDNA or anti-RNA binding protein antibodies at a single point in time. However, there was a poor correlation between changes in this score and changes in disease activity, C3 or anti-dsDNA antibody levels in patients followed longitudinally. In most patients the levels of IFN-induced gene expression remained relatively stable over 3–12 months despite marked changes in disease activity. Nevertheless, in patients with low/moderate disease activity, those with high IFN scores had a more recent history of sustained high disease activity.Conclusion:The findings indicate that IFN-induced gene expression has limited clinical utility as a biomarker of acute changes in disease activity.

scholarly journals The gene expression of type 17 T-helper cell-related cytokines in the urinary sediment of patients with systemic lupus erythematosus

Rheumatology ◽  
2009 ◽  
Vol 48 (12) ◽  
pp. 1491-1497 ◽  
Author(s):  
B. C.-H. Kwan ◽  
L.-S. Tam ◽  
K.-B. Lai ◽  
F. M.-M. Lai ◽  
E. K.-M. Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Systemic Lupus ◽  
Urinary Sediment

scholarly journals Positive Selection Affects the Expression of Systemic Lupus Erythematosus Associated Loci in Human Populations

2021 ◽  
Author(s):  
Victoria Oberreiter ◽  
Tobias Goellner ◽  
David L. Morris ◽  
Helmut Schaschl
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Positive Selection ◽  
Lupus Erythematosus ◽  
Lifestyle Changes ◽  
Genetic Ancestry ◽  
Selection Function ◽  
Human Populations ◽  
Systemic Lupus ◽  
A Genome

Abstract Background: Systemic lupus erythematosus (SLE) shows marked population-specific disparities in disease prevalence, including substantial variation in manifestations and complications according to genetic ancestry. Several recent studies suggest that a substantial proportion of variation of gene expression shows genetic ancestry-associated differences in gene regulation on immune responses. Positive selection may act in a population-specific manner on expression quantitative trait loci (eQTLs) and thereby contributes to the difference in the differences of SLE prevalence and manifestation in human populations. We tested the hypothesises that some of the identified SLE risk polymorphisms display pleiotropic effects or polygenicity driven by positive selection. We performed a genome-wide scan for recent positive selection by using integrated Haplotype Score (iHS) statistics in different human populations. In addition, we estimated the timing of beneficial mutations to understand what possible selective pressures drive positive selection at SLE-associated loci. Results: We identified several SLE risk loci that are population-specifically under positive selection. Almost all SNPs that are under positive selection function as cis-eQTLs in different tissue types. We determined that adaptive eQTLs affect the expression of fewer genes than non-adaptive eQTLs, suggesting a limited range of effect of an eQTL at SLE risk sites that show signatures of positive selection. Furthermore, some positively selected SNPs are located in transcription factor binding sequences. The timing of positive selection for the studied loci suggests that both environmental and recent lifestyle changes during as well as after the Neolithic Transition may have become selectively effective. We propose a novel link between positively selected eQTLs at a certain SLE risk locus in Europeans and a physiological pathway not previously considered in SLE.Conclusions: We conclude that population-specific adaptive eQTLs contribute to the observed variation in specific manifestations and complications of SLE in different ethnicities. Our results suggest also that human populations adapt more rapidly to environmental and lifestyle stimuli via modification of gene expression without having to alter the genetic code.

scholarly journals Systemic Lupus Erythematosus Disease: An Overview of the Clinical Approach to Pathogenesis, Diagnosis, and Treatment

2021 ◽  
Vol 4 (2) ◽  
pp. 91-98
Author(s):  
Saurabh Nimesh ◽  
Md. Iftekhar Ahmad ◽  
Shikhka Dhama ◽  
Pradeep Kumar ◽  
Muhammad Akram ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune System ◽  
Chronic Disease ◽  
Lupus Erythematosus ◽  
The Body ◽  
Clinical Approach ◽  
Systemic Lupus Erythematosus Disease ◽  
Systemic Lupus ◽  
Organ Systems ◽  
Novel Approaches

The systemic lupus erythematosus (SLE), commonly known as Lupus, is a rare and complex multisystem autoimmune disease where one’s immune system is overactive, and the body attacks its organ systems. SLE is a historically old disease described already in antiquity; it is an example of a chronic disease with physical, psychological, financial, and social implications for individuals diagnosed. It has inspired medical and basic biological scientists that focus on molecular biology, basic immunology, immunopathology, clinical science, genetics, and epidemiology. The syndrome is real in its existence-although hidden behind obstacles, cumbersome for patients and clinicians, and rebellious for scientists. There is currently no cure for SLE. The goal of treatment is to ease symptoms. This article will review information on the general approach to SLE therapy, focusing on currently approved therapies and novel approaches that might be used in the future.

scholarly journals Machine learning applied to whole-blood RNA-sequencing data uncovers distinct subsets of patients with systemic lupus erythematosus

2019 ◽  
Author(s):  
William A Figgett ◽  
Katherine Monaghan ◽  
Milica Ng ◽  
Monther Alhamdoosh ◽  
Eugene Maraskovsky ◽  
...  
Keyword(s):  
Gene Expression ◽  
Machine Learning ◽  
Systemic Lupus Erythematosus ◽  
Clinical Trials ◽  
Lupus Erythematosus ◽  
Whole Blood ◽  
Rna Seq ◽  
Systemic Lupus ◽  
Disease Heterogeneity ◽  
Healthy Donors

ABSTRACTObjectiveSystemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease that is difficult to treat. There is currently no optimal stratification of patients with SLE, and thus responses to available treatments are unpredictable. Here, we developed a new stratification scheme for patients with SLE, based on the whole-blood transcriptomes of patients with SLE.MethodsWe applied machine learning approaches to RNA-sequencing (RNA-seq) datasets to stratify patients with SLE into four distinct clusters based on their gene expression profiles. A meta-analysis on two recently published whole-blood RNA-seq datasets was carried out and an additional similar dataset of 30 patients with SLE and 29 healthy donors was contributed in this research; 141 patients with SLE and 51 healthy donors were analysed in total.ResultsExamination of SLE clusters, as opposed to unstratified SLE patients, revealed underappreciated differences in the pattern of expression of disease-related genes relative to clinical presentation. Moreover, gene signatures correlated to flare activity were successfully identified.ConclusionGiven that disease heterogeneity has confounded research studies and clinical trials, our approach addresses current unmet medical needs and provides a greater understanding of SLE heterogeneity in humans. Stratification of patients based on gene expression signatures may be a valuable strategy to harness disease heterogeneity and identify patient populations that may be at an increased risk of disease symptoms. Further, this approach can be used to understand the variability in responsiveness to therapeutics, thereby improving the design of clinical trials and advancing personalised therapy.

scholarly journals AB0541 Hepcidin and interferon-Α in systemic lupus erythematosus patients

2018 ◽  
Author(s):  
D. Archimandriti ◽  
A.T. Tzallas ◽  
T.-E. Memi ◽  
P. Spyrou ◽  
A.A. Drosos ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Interferon Α ◽  
Systemic Lupus
Sign in / Sign up

Export Citation Format

Share Document