scholarly journals Development and Validation of a MicroRNA Panel to Differentiate Between Patients with Rheumatoid Arthritis or Systemic Lupus Erythematosus and Controls

2019 ◽  
Vol 47 (2) ◽  
pp. 188-196 ◽  
Author(s):  
Michelle J. Ormseth ◽  
Joseph F. Solus ◽  
Quanhu Sheng ◽  
Fei Ye ◽  
Qiong Wu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Noncoding Rna ◽  
Characteristic Curve ◽  
Systemic Lupus ◽  
Control Subjects ◽  
Development And Validation ◽  
And Control ◽  
Bioinformatic Approach

Objective.MicroRNA (miRNA) are short noncoding RNA that regulate genes and are both biomarkers and mediators of disease. We used small RNA (sRNA) sequencing and machine learning methodology to develop an miRNA panel to reliably differentiate between rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) and control subjects.Methods.Plasma samples from 167 RA and 91 control subjects who frequency-matched for age, race, and sex were used for sRNA sequencing. TIGER was used to analyze miRNA. DESeq2 and random forest analyses were used to identify a prioritized list of miRNA differentially expressed in patients with RA. Prioritized miRNA were validated by quantitative PCR, and lasso and logistic regression were used to select the final panel of 6 miRNA that best differentiated RA from controls. The panel was validated in a separate cohort of 12 SLE, 32 RA, and 32 control subjects. Panel efficacy was assessed by area under the receiver operative characteristic curve (AUC) analyses.Results.The final panel included miR-22-3p, miR-24-3p, miR-96-5p, miR-134-5p, miR-140-3p, and miR-627-5p. The panel differentiated RA from control subjects in discovery (AUC = 0.81) and validation cohorts (AUC = 0.71), seronegative RA (AUC = 0.84), RA remission (AUC = 0.85), and patients with SLE (AUC = 0.80) versus controls. Pathway analysis showed upstream regulators and targets of panel miRNA are associated with pathways implicated in RA pathogenesis.Conclusion.An miRNA panel identified by a bioinformatic approach differentiated between RA or SLE patients and control subjects. The panel may represent an autoimmunity signature, perhaps related to inflammatory arthritis, which is not dependent on active disease or seropositivity.

scholarly journals Association study of TRAF1-C5 polymorphisms with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Japanese

2009 ◽  
Vol 69 (2) ◽  
pp. 368-373 ◽  
Author(s):  
K Nishimoto ◽  
Y Kochi ◽  
K Ikari ◽  
K Yamamoto ◽  
A Suzuki ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Association Study ◽  
Lupus Erythematosus ◽  
Case Control ◽  
Nucleotide Polymorphisms ◽  
Systemic Lupus ◽  
Control Series ◽  
Significant Difference ◽  
And Control

Objective:The primary aim of this study was to investigate the association of polymorphisms of TRAF1-C5, a newly identified rheumatoid arthritis (RA) risk locus in Caucasians, with susceptibility to RA and systemic lupus erythematosus (SLE) in Japanese populations. Gene expression levels of TRAF1 and C5 to assess the functional significance of genotypes were also analysed.Methods:A multicentre association study consisting of 4 RA case-control series (4397 cases and 2857 controls) and 3 SLE case-control series (591 cases and 2199 shared controls) was conducted. Genotyping was performed using TaqMan genotyping assay for two single nucleotide polymorphisms (SNPs) that showed the best evidence of association in the previous Caucasian studies. Quantifications of TRAF1 and C5 expression were performed with TaqMan expression assay.Results:Significant differences in allele frequency for both SNPs were observed between RA and control subjects (combined odds ratio  = 1.09), while no significant difference was detected between patients with SLE and controls. Interestingly, alleles rs3761847 A and rs10818488 G had increased the risk for RA in the present study, while they decreased the risk in the original studies. A significant difference was found between risk allele carriers and non-carriers of rs10818488 for the expression level of TRAF1 in phorbol myristate acetate-stimulated lymphoblastoid cell lines (p = 0.04).Conclusion:Association of TRAF1-C5 locus with RA susceptibility was detected in the Japanese populations with modest magnitude, while no significant association was observed for SLE. Significant positive effect of genotype on the expression of TRAF1 might support the genetic association between TRAF1 and RA.

scholarly journals Prognostic Impact of Genetic Variants of MECP2 and TIRAP on Clinical Outcomes of Systemic Lupus Erythematosus with and without Nephritis

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1378
Author(s):  
Safaa I. Tayel ◽  
Nashwa M. Muharram ◽  
Dina S. Fotoh ◽  
Hany S. Elbarbary ◽  
Huda I. Abd-Elhafiz ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Vitamin A ◽  
Lupus Erythematosus ◽  
Clinical Impact ◽  
Prognostic Impact ◽  
Laboratory Measurements ◽  
Systemic Lupus ◽  
Control Subjects ◽  
And Control ◽  
Personalize Medicine

Systemic lupus erythematosus (SLE) is a chronic autoimmune illness with a growing prevalence in many populations. Few studies have examined genetic predisposition to SLE, so we aimed to examine the clinical impact of the genetic polymorphisms MECP2 rs2734647and TIRAP rs8177374 on the outcomes and therapeutic precision of SLE with and without nephritis. This study included 110 SLE patients—divided into 63 with lupus nephritis (LN), and 47 without nephritis—and 100 controls. Laboratory measurements including CRP, ESR, ACR, CBC, anti-ds-DNA, vitamin A, C3, and C4 were carried out, along with genotyping of MECP2 rs2734647and TIRAP rs8177374 by real-time PCR and sequencing. Treg %, vitamin A, C3, and C4 were lower, whereas Th17 % was higher, in patients vs. controls (p < 0.001). The T allele of MECP2 rs2734647 was higher in LN than in non-nephritis and control subjects. Moreover, the T allele of TIRAP rs8177374 was higher in LN than in non-nephritis and control subjects. The MECP2 and TIRAP genes could play a role in predisposition to SLE, and can also predict disease progress to nephritis, helping to personalize medicine.

scholarly journals Association Between a History of Nontyphoidal Salmonella and the Risk of Systemic Lupus Erythematosus: A Population-Based, Case-Control Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Ting-Yu Tu ◽  
Chiu-Yu Yeh ◽  
Yao-Min Hung ◽  
Renin Chang ◽  
Hsin-Hua Chen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Multiple Sclerosis ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Case Control Study ◽  
Case Control ◽  
Systemic Lupus ◽  
Control Groups ◽  
And Control ◽  
Control Study

ObjectiveWe investigated the correlation between nontyphoidal Salmonella (NTS) infection and systemic lupus erythematosus (SLE) risk.MethodsThis case-control study comprised 6,517 patients with newly diagnosed SLE between 2006 and 2013. Patients without SLE were randomly selected as the control group and were matched at a case-control ratio of 1:20 by age, sex, and index year. All study individuals were traced from the index date back to their NTS exposure, other relevant covariates, or to the beginning of year 2000. Conditional logistic regression analysis was used to analyze the risk of SLE with adjusted odds ratios (aORs) and 95% confidence intervals (CIs) between the NTS and control groups.ResultsThe mean age was 37.8 years in the case and control groups. Females accounted for 85.5%. The aOR of having NTS infection were significantly increased in SLE relative to controls (aOR, 9.20; 95% CI, 4.51-18.78) in 1:20 sex-age matching analysis and (aOR, 7.47; 95% CI=2.08-26.82) in propensity score matching analysis. Subgroup analysis indicated that the SLE risk was high among those who dwelled in rural areas; had rheumatoid arthritis, multiple sclerosis, or Sjogren’s syndrome; and developed intensive and severe NTS infection during admission.ConclusionsExposure to NTS infection is associated with the development of subsequent SLE in Taiwanese individuals. Severe NTS infection and other autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, or Sjogren’s syndrome also contributed to the risk of developing SLE.

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