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Positive correlation of STAT1 and miR-146a with anemia in patients with systemic lupus erythematosus.

ABSTRACT: Anemia is one of the most common hematological manifestations in SLE patients, occurring in about 50% of active cases. STAT1 is a critical signaling molecule required for the production of type-1 interferon (I-IFN), CCL2, and CXCL10, all of which are upregulated in SLE. Overexpression of STAT1 has been described to be involved in anemia in animal models. The aim of this study is to analyze how these components are involved in SLE-associated anemia.Blood samples were collected from 39 healthy donors and 101 SLE patients fulfilling ACR criteria. Samples were collected from a total of 180 visits (58 patients had 2 or more visits) of which 52 visits included a diagnosis of anemia. Healthy donors had only single visit. Total RNA, isolated from leukocytes, was analyzed by Taqman qPCR. Relative expression levels of I-IFN signature genes, chemokines, and miR-146a were determined by the ??CT method. Results were correlated with clinical data and analyzed by the Wilcoxon/Kruskal-Wallis test and Fisher's exact test.Significant increases in IFN score (p < 0.0001), STAT1 (p < 0.0001), miR-146a (p < 0.0005), CCL2 (p = 0.0047), and CXCL10 (p = 0.017), as well as a significant decrease in pri-miR-146a (p = 0.0002), were detected in the anemic SLE patient visits (n = 52) compared to non-anemic SLE visits (n = 128). Regardless of disease activity, lupus nephritis, or race, anemic SLE patients displayed significantly elevated levels of STAT1 and miR-146a compared to non-anemic SLE patients.STAT1 and miR-146a may be upregulated during inflammation and via proinflammatory cytokines and chemokines in SLE. Prolonged upregulation of STAT1 and miR-146a appears to play an important role in anemia in SLE patients.

SUBMITTER: Dominguez-Gutierrez PR

PROVIDER: S-EPMC3943692 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Positive correlation of STAT1 and miR-146a with anemia in patients with systemic lupus erythematosus.

Dominguez-Gutierrez Paul R PR Ceribelli Angela A Satoh Minoru M Sobel Eric S ES Reeves Westley H WH Chan Edward K L EK

Journal of clinical immunology 20131201 2

<h4>Purpose</h4>Anemia is one of the most common hematological manifestations in SLE patients, occurring in about 50% of active cases. STAT1 is a critical signaling molecule required for the production of type-1 interferon (I-IFN), CCL2, and CXCL10, all of which are upregulated in SLE. Overexpression of STAT1 has been described to be involved in anemia in animal models. The aim of this study is to analyze how these components are involved in SLE-associated anemia.<h4>Methods</h4>Blood samples we ...[more]

PMID: 24292724

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Project description:Background and objectivemiRNA-146a is a microRNA that plays an important role in systemic lupus erythematosus (SLE). Several studies have examined the role of miRNA-146a in SLE, but have demonstrated equivocal or even contradictory conclusions. Therefore, this meta-analysis aimed to assess the role of miRNA-146a in SLE by examining data from previous studies.MethodsA meta-analysis of relevant papers published before August 31, 2019, in the WanFang, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), PubMed, EMBASE, and Web of Science databases was performed to verify the relationship of miRNA-146a expression level to SLE. Two investigators independently extracted the data and conducted a quality assessment of the studies. All statistical analyses were performed using Stata 14.0. Trial sequence analysis (TSA) was conducted to assess the quality and strength of the studies using the TSA software.ResultsSix publications, involving 151 SEL patients and 132 healthy individuals as controls were included in this meta-analysis. The results showed that the expression of miRNA-146a was associated with SLE risk [standard mean difference (SMD) = -1.21, 95% confidence interval (95% CI) (-2.18, -0.23), P = .015]. The stratified analysis revealed that the expression of miRNA-146a was highly related to higher SLE risk among Asian (SMD = -1.30, 95% CI (-2.52, -0.07), P = .038) and Caucasian (SMD = -0.72, 95% CI (-1.20, -0.24), P = .003) populations. Besides, the serum levels of miRNA146a were significantly different (SMD = -1.73, 95% CI (-3.11, -0.36), P = .014). The TSA revealed that the cumulative Z-curve crossed the typical boundary value, and reached the TSA monitoring boundary, but did not reach the required information size. This indicates that even if the cumulative sample size did not meet required information size, no more trials were needed and a reliable conclusion was reached in advance. Sensitivity analyses indicated the instability of the meta-analysis.ConclusionsOverall, the expression of miRNA-146a is associated with SLE risk. Therefore, miRNA-146a is a promising candidate for the effective diagnosis of SLE. But, due to the limitations of this study, it is necessary to cautiously explain the results of this study.Systematic review registrationPROSPERO CRD42019151381.

Dataset Information

Positive correlation of STAT1 and miR-146a with anemia in patients with systemic lupus erythematosus.

Publications

Positive correlation of STAT1 and miR-146a with anemia in patients with systemic lupus erythematosus.

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