scholarly journals AB0015 IDENTIFICATION OF KEY GENES TO SUPPORT SYSTEMIC LUPUS ERYTHEMATOSUS, RHEUMATOID ARTHRITIS AND ANKYLOSING SPONDYLITIS DIAGNOSIS BY TRANSCRIPTOMIC APPROACH

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1311.2-1311
Author(s):  
A. Mashayekhi Sardoo ◽  
P. Leo ◽  
M. Santos ◽  
T. Costa ◽  
S. F. Almeida ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Early Diagnosis ◽  
Lupus Erythematosus ◽  
Peripheral Blood ◽  
Inflammatory Rheumatic Diseases ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Early Therapy ◽  
Asas Criteria

Background:Early diagnosis of inflammatory rheumatic diseases (IRD), as Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA) and axial Spondyloarthritis (axSpA) represents in our days a major clinical challenge. Increasing evidence has determined that early diagnosis, prompt treatment initiation and early achievement of remission are the best predictors of long-term clinical, functional and radiographic outcomes. Therefore, identification of sensitive biomarkers to support an early diagnosis to enable early therapy is of utmost importance [1,2].Objectives:This study aims to identify novel genes that may improve the current clinical diagnosis approach for early SLE, RA and axSpA.Methods:A cross-sectional study was conducted on 44 participants, 12 with axSpA (according to ASAS criteria), 11 with RA (according to ACR/EULAR criteria for RA), 10 with SLE (according to ACR classification criteria for SLE) and 11 Healthy Controls (HC), gender and age matched. Patients with co-occurrence of other IRD or having received biological therapies were excluded. Peripheral blood samples were collected into PAXgene tubes and stored in -80°C. mRNA profiling by RNA-seq was performed. Unpaired t-tests with multivariate permutation correction were applied to identify differentially expressed genes (DEGs) between patients and HC for each disease and within diseases. Enrichment analysis, Gene ontology (GO) and Kyoto Enrichment of Genes and Genomes (KEGG) analysis were also performed. DEGs that allow to distinguish each disease from HC and between diseases. The top DEGs (axSpA n=2, RA n=2, SLE n=3) identified were confirmed by quantitative RT-PCR.Results:For axSpA, genes involved in negative regulation of cytokines by JAK/STAT pathway and in osteoblast differentiation through STAT3 pathway, were confirmed. In SLE, genes involved in trap for immune complexes in peripheral blood and involved in nucleosome regulation, were also confirmed. Regarding RA, no genes were confirmed.Conclusion:Our work provides new insights into IRD pathogenesis, and discloses new biomarkers, which may be useful as either predictive biomarkers for diagnosis or therapeutic targets to improve IRD approach.Further validation are needed in different cohorts.References:[1]Monti, S. et al. (2015) ‘Rheumatoid arthritis treatment: The earlier the better to prevent joint damage’, RMD Open, 1(Suppl 1), pp. 1–5. doi: 10.1136/rmdopen-2015-000057.[2]Oglesby, A. et al. (2014) ‘Impact of early versus late systemic lupus erythematosus diagnosis on clinical and economic outcomes.’, Applied health economics and health policy, 12(2), pp. 179–90. doi: 10.1007/s40258-014-0085-x.Acknowledgments:To all patients and healthy controls who participated in the studyDisclosure of Interests:Atlas Mashayekhi Sardoo: None declared, Paul Leo: None declared, Mariana Santos: None declared, Tiago Costa: None declared, Sergio Fernandes Almeida: None declared, Sara Maia: None declared, Vladimir Benes: None declared, Mattew Brown Speakers bureau: MSD, Pfizer, Novartis, Jaime Branco Speakers bureau: Vitoria, Fernando Pimentel dos Santos Speakers bureau: Novartis, Pfizer, Biogen, Vitoria,

scholarly journals Novel gene variants associated with cardiovascular disease in systemic lupus erythematosus and rheumatoid arthritis

2018 ◽  
Vol 77 (7) ◽  
pp. 1063-1069 ◽  
Author(s):  
Dag Leonard ◽  
Elisabet Svenungsson ◽  
Johanna Dahlqvist ◽  
Andrei Alexsson ◽  
Lisbeth Ärlestig ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Cardiovascular Disease ◽  
General Population ◽  
Lupus Erythematosus ◽  
Risk Allele ◽  
Snp Array ◽  
Inflammatory Rheumatic Diseases ◽  
Systemic Lupus ◽  
Increased Risk

ObjectivesPatients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) have increased risk of cardiovascular disease (CVD). We investigated whether single nucleotide polymorphisms (SNPs) at autoimmunity risk loci were associated with CVD in SLE and RA.MethodsPatients with SLE (n=1045) were genotyped using the 200K Immunochip SNP array (Illumina). The allele frequency was compared between patients with and without different manifestations of CVD. Results were replicated in a second SLE cohort (n=1043) and in an RA cohort (n=824). We analysed publicly available genetic data from general population, performed electrophoretic mobility shift assays and measured cytokine levels and occurrence of antiphospholipid antibodies (aPLs).ResultsWe identified two new putative risk loci associated with increased risk for CVD in two SLE populations, which remained after adjustment for traditional CVD risk factors. An IL19 risk allele, rs17581834(T) was associated with stroke/myocardial infarction (MI) in SLE (OR 2.3 (1.5 to 3.4), P=8.5×10−5) and RA (OR 2.8 (1.4 to 5.6), P=3.8×10−3), meta-analysis (OR 2.5 (2.0 to 2.9), P=3.5×10−7), but not in population controls. The IL19 risk allele affected protein binding, and SLE patients with the risk allele had increased levels of plasma-IL10 (P=0.004) and aPL (P=0.01). An SRP54-AS1 risk allele, rs799454(G) was associated with stroke/transient ischaemic attack in SLE (OR 1.7 (1.3 to 2.2), P=2.5×10−5) but not in RA. The SRP54-AS1 risk allele is an expression quantitative trait locus for four genes.ConclusionsThe IL19 risk allele was associated with stroke/MI in SLE and RA, but not in the general population, indicating that shared immune pathways may be involved in the CVD pathogenesis in inflammatory rheumatic diseases.

TCONS_00483150 as a novel diagnostic biomarker of systemic lupus erythematosus

Epigenomics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 973-988
Author(s):  
Gangqiang Guo ◽  
Aqiong Chen ◽  
Lele Ye ◽  
Huijing Wang ◽  
Zhiyuan Chen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Noncoding Rnas ◽  
Differentially Expressed ◽  
Healthy Controls ◽  
Diagnostic Biomarker ◽  
Systemic Lupus ◽  
Functional Roles ◽  
Antibody Positivity

Aim: We aimed to identify differentially expressed Long noncoding RNAs (lncRNAs) and explore their functional roles in systemic lupus erythematosus (SLE). Materials & methods: We identified dysregulated lncRNAs and investigated their prognostic values and potential functions using MiRTarget2, catRAPID omics and Bedtools/blast/Pearson analyses. Results: Among the 143 differentially expressed lncRNAs, TCONS_00483150 could be used to distinguish patients with SLE from healthy controls and those with rheumatoid arthritis and patients with active/stable SLE from healthy controls. TCONS_00483150 was significantly correlated with anti-Rib-P antibody positivity and low C3 levels; TCONS_00483150 dysregulation might contribute to the metabolism of RNA and proteins in SLE patients. Conclusion: Overall, our findings offer a transcriptome-wide overview of aberrantly expressed lncRNAs in patients with SLE and highlight TCONS_00483150 as a potential novel diagnostic biomarker.

scholarly journals Interpretation of ANA Indirect Immunofluorescence Test Outside the Darkroom Using NOVA View Compared to Manual Microscopy

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Susan S. Copple ◽  
Troy D. Jaskowski ◽  
Rashelle Giles ◽  
Harry R. Hill
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Healthy Controls ◽  
Immunofluorescence Test ◽  
Systemic Lupus ◽  
Future Studies ◽  
Indirect Immunofluorescence Test ◽  
Fluorescent Microscope ◽  
Medical Technologist

Objective.To evaluate NOVA View with focus on reading archived images versus microscope based manual interpretation of ANA HEp-2 slides by an experienced, certified medical technologist.Methods.369 well defined sera from: 44 rheumatoid arthritis, 50 systemic lupus erythematosus, 35 scleroderma, 19 Sjögren’s syndrome, and 10 polymyositis patients as well as 99 healthy controls were examined. In addition, 12 defined sera from the Centers for Disease Control and 100 random patient sera sent to ARUP Laboratories for ANA HEp-2 IIF testing were included. Samples were read using the archived images on NOVA View and compared to results obtained from manual reading.Results.At a 1 : 40/1 : 80 dilution the resulting comparison demonstrated 94.8%/92.9% positive, 97.4%/97.4% negative, and 96.5%/96.2% total agreements between manual IIF and NOVA View archived images. Agreement of identifiable patterns between methods was 97%, with PCNA and mixed patterns undetermined.Conclusion.Excellent agreements were obtained between reading archived images on NOVA View and manually on a fluorescent microscope. In addition, workflow benefits were observed which need to be analyzed in future studies.

scholarly journals AB0002 ASSOCIATION OF C1Q GENETIC POLYMORPHISMS WITH SUSCEPTIBILITY TO RHEUMATOID ARTHRITIS IN BULGARIAN COHORT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1036.3-1036
Author(s):  
M. Kosturkova ◽  
G. Mihaylova ◽  
M. Radanova
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Autoimmune Diseases ◽  
Gene Cluster ◽  
Lupus Erythematosus ◽  
Annual Review ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Allelic Discrimination Assay ◽  
Increased Risk

Background:Complement is strongly implicated in the pathogenesis of autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Its component C1q plays a dualistic role, triggering the inflammatory cascade on one hand and directing the clearance of immune complexes on the other. Homozygous genetic deficiency of C1q is strongly associated with SLE and SLE-like phenotype as almost 90% of C1q deficient individuals develop SLE or similar disease. Nevertheless, there are few and inconsistent studies exploring the single nucleotide polymorphisms (SNPs) of the C1q gene cluster in relation to the pathogenesis of SLE and RA.Objectives:The aim of the study was to evaluate the possible association of five SNPs – rs292001, rs172378, rs294179, rs665691 and rs682658 in complement C1q gene cluster with susceptibility to SLE and RA in Bulgarian cohort.Methods:Fifty patients with SLE, sixty-one patients with RA and sixty-seven healthy controls were genotyped for the five SNPs by TaqMan allelic discrimination assay.Results:Frequency of genotypes and alleles of rs294179, rs665691 and rs682658 SNPs was similar between patients with SLE, RA and healthy controls. For rs172378 SNP, the minor G allele (OR = 2.73; 95% CI, 1.59-4.67, p=0.0003) and GG genotype (OR = 5.12; 95% CI, 1.60-16.49, p=0.006) were associated with susceptibility to RA. In our cohort in accordance with others, AA rs292001 SNP genotype was associated with increased risk for RA (OR = 3.32; 95% CI, 1.19-9.20, p=0.021). For SLE patients, AA rs292001 SNP genotype was low presented and did not associate with disease.Conclusion:GG genotype of rs172378 SNP in C1q gene cluster could be considered as a new risk factor for RA.References:[1]Diane Scott et al (2016). The paradoxical roles of C1q and C3 in autoimmunity. Immunobiology, 719-25. doi:10.1016/j.imbio.2015.05.001.[2]Giles JL et al (2015). Functional analysis of a complement polymorphism (rs17611) associated with rheumatoid arthritis. J Immunol., 3029-34. doi:10.4049/jimmunol.1402956.[3]Holers, V. M. (2018). Complement in the Initiation and Evolution of Rheumatoid Arthritis. Frontiers in immunology, 1057. doi:10.3389/fimmu.2018.01057.[4]Lintner, K. E. (2016). Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases. Frontiers in immunology, 36. doi:10.3389/fimmu.2016.00036.[5]Lu, J. &. (2017). C1 Complex: An Adaptable Proteolytic Module for Complement and Non-Complement Functions. Frontiers in immunology, 592. doi:10.3389/fimmu.2017.00592.[6]Manderson, A. P. (2004). The role of complement in the development of systemic lupus erythematosus. Annual review of immunology, 431-456. doi:10.1146/annurev.immunol.22.012703.104549.[7]Martens, H. A. (2009). Analysis of C1q polymorphisms suggests association with systemic lupus erythematosus, serum C1q and CH50 levels and disease severity. Annals of the rheumatic diseases, 715–720. doi:10.1136/ard.2007.085688.[8]Namjou B, G.-M. C. (2009). Evaluation of C1q genomic region in minority racial groups of lupus. Genes Immun., 517-24. doi:10.1038/gene.2009.33.[9]Radanova M et al(2015). Association of rs172378 C1q gene cluster polymorphism with lupus nephritis in Bulgarian patients. Lupus, 280-9. doi:10.1177/0961203314555173.[10]Rafiq S et al (2010). Assessing association of common variation in the C1Q gene cluster with systemic lupus erythematosus. Clin Exp Immunol., 284-9. doi:10.1111/j.1365-2249.2010.04185.x.[11]Schejbel L et al (2011). Molecular basis of hereditary C1q deficiency-revisited: identification of several novel disease-causing mutations. Genes Immun., 626-634.[12]Trouw LA et al (2013). Genetic variants in the region of the C1q genes are associated with rheumatoid arthritis. Clin Exp Immunol., 76-83. doi:10.1111/cei.12097.[13]Trouw L. A. (2017). The complement system as a potential therapeutic target in rheumatic disease. Nature reviews. Rheumatology, 538–547. doi:10.1038/nrrheum.2017.125.[14]Walport M. J. (2002). Complement and systemic lupus erythematosus. Arthritis research, S279–S293. doi:10.1186/ar586.Disclosure of Interests:None declared

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