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Objective:To investigate the impact and interaction of Toll like receptor 2 (TLR2) and interferon regulatory factor 5 (IRF-5) gene polymorphisms on the susceptibility to neonatal sepsis.Methods:A total of 78 cases of neonatal septicemia patients admitted to Baoding Children′s Hospital from July 2018 to August 2021 were prospectively selected as the study group, and 78 cases of healthy newborns in the same period were selected as the control group. The TLR2 and IRF-5 gene polymorphisms and the levels of inflammatory markers [C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in different genotypes of infants were compared between the two groups. We evaluated the relationship between TLR2 and IRF-5 genotypes, inflammatory markers, and susceptibility to neonatal sepsis, and analyzed the interaction between their gene polymorphisms and susceptibility to neonatal sepsis.Results:There were significant differences in the distribution of TLR2 (rs3804099) and IRF-5 (rs2004640) loci genotype and Allele frequency between the two groups (all P<0.05); The serum CRP, TNF-α, and IL-6 levels in children with TLR2 (rs3804099) genotype TT genotype [(111.12±30.87)mg/L, (77.50±20.02)pg/ml, (40.27±11.31)pg/ml] were higher than those in children with CC/CT genotype [(72.46±24.51)mg/L, (54.18±17.65)pg/ml, (28.34±9.05)pg/ml], and the differences were statistically significant (all P<0.05). The serum CRP, TNF-α, and IL-6 levels [(113.90±28.94)mg/L, TNF-α (79.84±19.82)pg/ml, IL-6 (41.05±11.49)pg/ml] in children with the IRF-5 (rs2004640) TT genotype were higher than those in children with the GG/GT genotype [(70.88±22.16)mg/L, (52.27±16.73)pg/ml, (27.96±9.75)pg/ml], and the differences were statistically significant (all P<0.05). The TT genotypes at TLR2 (rs3804099) and IRF-5 (rs2004640) loci were positively correlated with serum CRP, TNF-α, and IL-6 levels (all P<0.05); The TT genotypes at TLR2 (rs3804099) and IRF-5 (rs2004640) loci were independent risk factors for susceptibility to neonatal sepsis (all P<0.05); The TT genotype at the TLR2 (rs3804099) locus and the TT genotype at the IRF-5 (rs2004640) locus exhibited a positive interaction in susceptibility to neonatal sepsis ( OR=7.467, γ=1.728). Conclusions:TLR2 (rs3804099) TT genotype and IRF-5 (rs2004640) TT genotype significantly increase the susceptibility to neonatal sepsis, and there is a positive interaction between the two.
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Background & objectives: Genetic aberrations disrupting toll-like receptor and interferon homeostasis enhance the risk of systemic lupus erythematosus (SLE). Raised serum interferon-alpha (IFN-?) levels in SLE patients have been ascribed to polymorphism (rs2004640 G/T) in interferon regulatory factor 5 (IRF5) gene, resulting in enhanced transcript splicing. A positive association between IRF5 polymorphism and SLE risk has been reported in many populations. This study was aimed to find out frequency of IRF5 rs2004640 G/T polymorphism in patients with SLE and healthy controls and to assess its influence on susceptibility, clinical and serological characteristics of SLE. Methods: IRF5 rs2004640 (G/T) polymorphism was analyzed in 300 SLE patients and 460 age and sex matched controls by real-time PCR. Results: The IRF5 rs2004640 (G/T) polymorphism did not confer risk of SLE or influence clinical or serological phenotype. However, the mutant allele conferred a borderline risk to develop thrombocytopenia (odds ratio: 2.05, 95% confidence interval: 0.97�3, P=0.06) in patients with SLE. Interpretation & conclusions: Our study revealed that the IRF5 rs2004640 polymorphism was not a risk factor for SLE in population from south India. It may, however, be a useful genetic marker for thrombocytopenia in SLE patients. Although we could not demonstrate susceptibility toward lupus in the presence of IRF5 rs2004640 (G/T) polymorphism, further exploration of the genetic variability of IRF5 may help uncover its pathogenic role in Indian SLE patients.
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ObjectiveTo investigate the correlation between interferon regulatory factor 5 (IRF5) ,vitamin D receptor (VDR ) ,beta-defensin 1 (DEFB1 ) ,Toll-like receptor 4 (TLR4 ) gene polymorphismand Crohn′s disease (CD) in Chinese Han population .MethodsFrom January 2007 to May 2011 ,thedata and serum samples of 158 CD patients and 246 healthy controls were collected .The genotype of 14tag single-nucleotide polymorphisms (SNP) of IRF5 ,VDR ,DEFB1 and TLR4 were detected .Chi-squaretest was performed for rate comparison between CD group and healthy control group . Multifactordimensionality reduction (MDR) was used to analyze the combined effects of above candidate genes and therelation with susceptibility of CD .ResultsAccording to allele or genotype correlation analysis ,there wasno correlation between IRF5 ,VDR ,DEFB1 ,TLR4 and susceptibility of CD (all P> 0 .05) .The resultsof haplotype correlation analysis indicated that the frequency of GTACC haplotype in IRF5 of CD groupand healthy control group was 0 .046 and 0 .089 ,respectively ,the difference was statistically significant (χ2 = 5 .223 ,P= 0 .022 3) .The results of genotype and clinical type analysis indicated that the genotypesof rs2978880 of DEFB1 in CD patients were C/C ,C/T ,T/T ,the frequency of patients with surgery was0 .235 ,0 .603 and 0 .162 ,respectively ,and the frequency of patients without surgery was 0 .482 ,0 .388and 0 .129 ,respectively .The risk of intestinal surgery in patients with C /C genotype was lower (χ2 =10 .065 ,P= 0 .006 ) .The results of MDR analysis indicated that no interactions were detected betweenabove genes and susceptibility of CD (all P > 0 .05) .ConclusionsThe GTACC haplotype in IRF5 wascorrelated with the susceptibility of CD ,and the C/C genotype of rs2978880 of DEFB1 was correlatedwith CD clinical phenotype in Chinese Han population .
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Interferon regulatory factor 5 (IRF-5) can induce the expressions of IFN-α,IFN-β and promote the secretion of cytokines,including IL-6,IL-12 b,IL-17,IL-23,TNF etc.IRF-5 is involved in the process of immune response,cell growth,cell differentiation,cell apoptosis,tumorigenesis and cell signal transduction.For that reason,IRF-5 plays an important role in the occurrence and progress of many diseases in humans.Further studies of IRF-5 will better elucidate the pathogenesis of related diseases and provide theoretical basis for treatment of these diseases and the corresponding therapeutic targets.
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Objective To investigate the mRNA expression of toll like receptor-9 (TLR9) and interferon regulatory factors-5 (IRF5) of AS2O3 on peripheral blood mononuclear cells (PBMCs) in systemic lupus erythematosus (SLE) patients.Methods PBMCs of 15 SLE patients and 15 healthy subjects were treated with different concentrations of AS2O3 and cyclophosphamide (CTX) in vitro.Real-time quantitative polymerase chain reaction was used to amplify TLR9 and IRF5 gene before and after 12 and 24 hours drug intervention and the mRNA expressions were measured.Differences between groups were analyzed by paired t test or variance analysis.Results The mRNA expression levels of TLR9 [12 h(1.38±0.26) and 24 h (1.28±0.35)] on PBMCs in SLE patients were significantly higher than those in healthy controls [12 h(1.05±0.35) and 24 h (0.97±0.19)](t=2.37,P=0.03; t=2.44,P=0.02).The IRF5 mRNA expression levels [12 h (0.95±0.27) and 24 h (0.91 ±0.35)] in SLE patients were obviously higher than those in healthy controls [12 h (0.62 ±0.23) and 24 h (0.60±0.39)] (t =3.07,P=0.01 ; t =3.45,P＜0.01).AS2O3 could suppress the mRNA expression of TLR9 on PBMCs and the effect was gradually increasing with the increasing concentration of AS2O3 and processing time [0.2 mg/L AS2O3 group 12 h (0.430±0.110) and 24 h(0.290±0.050),0.4 mg/L AS2O3 group 12 h (0.170±0.038) and 24 h (0.090±0.017),0.8 mg/L AS2O3 group 12 h (0.023±0.011) and 24 h (0.003±0.001)].Comparing with CTX [12 h (0.814±0.081) and 24 h(0.755±0.139)],AS2O3 had a more significant strong effect on inhibiting the expression of TLR9 mRNA in SLE patients [F=165.32(12 h),P＜0.01; F=99.20 (24 h),P＜0.01].The mRNA expression of IRF5 on PBMCs was not suppressed by AS2O3 and CTX and there was no statistically significant difference between groups (P＞0.05).Conclusion There is abnormal expression of IRF5 and TLR9 mRNA in SLE patients.AS2O3 may suppress the TLR9 mRNA expression in SLE patients,which may be one mechanism of clinical effectiveness.
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h may play a role in the pathogenesis of SLE.
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Objective To compare the expression level of interferon regulator factor 5 (IRF5) of the health controls and systemic lupus erythematosus (SLE) patients and analyze the relationship between IRF5 and SLE disease activity. Methods Peripheral blood monoeytes (PBMCs) from SLE patients and healthy donors were separated with Ficoll density gradient eentrifugation and total cellular RNA was isolated with Trizol from the PBMCs, the mRNA was reverse transcripted to cDNA. Real-time PCR was applied to determine the expression level of IRFS. The expression level of IRF5 between the two groups were compared. The correlations of expression level of IRF5 with SLE disease activity and other laboratory or clinical parameters of SLE patients were analyzed. Results The level of IRF5 was (2.1±2.2) in SLE patients and (1.5±1.2) in healthy controls, the difference was not statistically significant (P=0.161). And the levels of IRF5 in SLE patients were significantly correlated with their SLEDAI (r=0.616,P<0.01), but not correlated with other parameters such as bemoglobulin complements, immunoglobulin etc. Anti-dsDNA antibody positive patients had significantly higher expression of IRF5 compared to the anti-dsDNA-antibedy-negative patients. The IRF5 mRNA levels of SLE patients with fever or neuropsyehiatric symptoms were significantly higher than those of patients free of neuropsychiatrie involvement. Conclusion High expression level of 1RF5 may contribute to the pathogenesis of SLE in disease activity and antibody production.