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. 2016 Mar 8:7:56.
doi: 10.3389/fimmu.2016.00056. eCollection 2016.

miR-146a and miR-155 Expression Levels in Acute Graft-Versus-Host Disease Incidence

Sadaf Atarod  1 , Mohammed Mahid Ahmed  1 , Clare Lendrem  1 , Kim Frances Pearce  1 , Wei Cope  1 , Jean Norden  1 , Xiao-Nong Wang  1 , Matthew Collin  1 , Anne Mary Dickinson  1
Affiliations

miR-146a and miR-155 Expression Levels in Acute Graft-Versus-Host Disease Incidence

Sadaf Atarod et al. Front Immunol. .

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for numerous hematological malignancies. However, acute graft-versus-host disease (aGVHD) is still the major complication causing mortality. MicroRNAs (miRNAs) play a significant role in inflammation and have potential as prognostic and diagnostic biomarkers. This study investigated the role of two immune-specific miRNAs (miR-146a and miR-155) as biomarkers for aGVHD incidence in the peripheral blood of allo-HSCT patients prior to disease onset. The study showed that miR-146a and its statistical interaction with miR-155 at day +28 were predictive of aGVHD incidence. Interestingly, the expression levels of miR-146a and miR-155 negatively correlated with the transcription factor, SPI1 (PU.1gene) mRNA expression.

Keywords: acute graft-versus-host disease; allogeneic hematopoietic stem cell transplantation; biological markers; graft-versus-host disease; microRNAs.

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Figures

Figure 1
Figure 1
Under-expression of miR-146a-5p and miR-155-5p leads to a higher probability of aGVHD incidence. The graph demonstrates the miR-146a-5p and miR-155-5p expression levels at day +28, dichotomized based on aGVHD incidence (0 = no GVHD and 1 = aGVHD grades I–III). The straight-line shows the median expression levels in this cohort (n = 54) for miR-146a-5p (−3.845) and miR-155-5p (−4.585).
Figure 2
Figure 2
miR-155-5p and miR-146a-5p expression directly correlated with SPI1 mRNA levels. There was a significant negative correlation for both (A) miR-155-5p and (B) miR-146a-5p expression. The correlation was only significant in aGVHD patients with grades I–III (n = 27). The x-axis shows the miRNA expression levels and the y-axis the SPI1 mRNA levels. Spearman correlation was used to test for correlation. Spearman rho: rs. Significance level was set at p ≤ 0.05.
Figure 3
Figure 3
miR-146a-5p and miR-155-5p mechanism of action under normal conditions and early stages of inflammation (2, 9, 34). During the early stages of inflammation in GVHD, the TLR and Janus Kinase (JAK)-STAT1 pathway are activated by LPS and IFN-γ, respectively. Under such conditions, miR-146a-5p and miR-155-5p have reduced expression levels. This results in minor alterations of the mRNA target levels and may therefore represent subclinical early inflammatory GVHD.
See this image and copyright information in PMC

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