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Objective:To investigate the role of miR-146a in the pathogenesis of systemic juvenile idiopathic arthritis (sJIA) and its clinical significance.Methods:This article is a prospective clinical cohort study.Twenty-six patients with sJIA (14 cases of initial active group and 12 cases of stable group), 15 patients with multijoint juvenile idiopathic arthritis (JIA) and 15 patients with oligojoint JIA diagnosed in the Department of Rheumatology and Immunology of Anhui Provincial Children′s Hospital from June 2018 to December 2020 were enrolled.Twenty healthy controls from the out-patient clinic were also recruited.The expression level of miR-146a in peripheral blood mononuclear cells (PBMCs) of research objects was detected by real-time fluorescence quantitative polymerase reaction (qPCR), and the serum levels of interleukin (IL) - 6, tumor necrosis factor (TNF) - α and IL-1β in sJIA patients and healthy controls were detected by enzyme-linked immunosorbent assay.The expression levels of miR-146a in PBMCs and cytokines among different groups were compared by analysis of variance. Pearson correlation analysis was used to analyze the correlation of the relative expression level of miR-146a in PBMCs with clinical inflammatory indexes and serum cytokines in sJIA patients. Results:(1) The expression level of miR-146a in PBMCs of early sJIA patients was significantly higher than that in the multijoint JIA group and oligojoint JIA group (8.77±3.15 vs.4.40±1.59, 2.55±1.15, t=6.27, 14.23; all P<0.05). The expression level of miR-146a in PBMCs of sJIA active patients was significantly higher than that in sJIA stable patients (8.77±3.15 vs.3.63±1.37, t=10.27, P<0.05). There was no significant difference in the expression level of miR-146a between the sJIA stable group and healthy control group ( P>0.05). (2) The expression levels of IL-1β, IL-6 and TNF-α were significantly higher in sJIA active patients group than those in sJIA stable group[(58.56±17.47) ng/L vs.(26.32±10.54) ng/L, (73.72±11.16) ng/L vs.(23.20±9.12) ng/L, (70.93±19.97) ng/L vs.(24.25±9.49) ng/L, all P<0.05]. There was no significant difference in the expression levels of IL-1β, IL-6 and TNF-α between the sJIA stable group and healthy control group(all P>0.05). (3)The expression of miR-146a in PBMCs of sJIA patients was positively correlated with serum ferritin levels, platelets, erythrocyte sedimentation rates, C-reactive proteins, IL-1β, IL-6 and TNF-α( r=0.542, 0.433, 0.329, 0.306, 0.333, 0.342, 0.319, all P<0.05). Conclusions:miR-146a may be involved in the inflammatory process of sJIA disease.miR-146a can well distinguish sJIA from multijoint JIA and oligojoint JIA.TNF-α, IL-1β and IL-6 are involved in sJIA inflammatory responses.
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OBJECTIVE@#To detect variant of TRNT1 gene in a child featuring sideroblastic anemia with B-cell immunodeficiency, periodic fever and developmental delay (SIFD).@*METHODS@#The proband and his parents were analyzed through trio-whole exome sequencing. Sanger sequencing and bioinformatic analysis were carried out to verify the candidate variant sites associated with the clinical phenotype.@*RESULTS@#Genetic testing showed that the proband has carried compound heterozygous variants of the TRNT1 gene, namely c.88A>G(p.Met30Val) and c.363G>T(p.Glu121Asp). Sanger sequencing confirmed that the variants were respectively inherited from his father and mother. The variants were unreported previously. By bioinformatic analysis, both variants were predicted to affect the stability of binding of the TRNT1 protein with tRNA. Based on the American College of Medical Genetics and Genomics standards and guidelines, c.88A>G and c.363G>T variants of TRNT1 gene were predicted to be uncertain significance (PM2+PP3+PP4) and likely pathogenic (PM1+PM2+PP3+PP4), respectively.@*CONCLUSION@#The c.88A>G (p.Met30Val) and c.363G>T(p.Glu121Asp) compound heterozygous variants of the TRNT1 gene probably underlay the disease in this patient. Above finding has enriched the spectrum of TRNT1 gene variants.