Plasma microRNA-586 is a new biomarker for acute graft-versus-host disease

Abstract

Acute graft-versus-host disease (aGVHD) is one of the major causes of morbidity and mortality in patients receiving allogeneic hematopoietic cell transplantation (allo-HSCT). MicroRNAs (miRs) were found to have the potential to be the new biomarkers of aGVHD. In this study, we collected samples from 98 patients who underwent allo-HSCT; 63 patients developed aGVHD, and 35 patients did not. Plasma samples were collected at three time points (before aGVHD, at the onset of aGVHD, and after aGVHD) from 52 patients, and the miR-586 expression level was detected by quantitative real-time PCR. We found that the plasma miR-586 level was decreased at the onset of grade I-II aGVHD (P = 0.074). In contrast, when infections were detected, plasma miR-586 level was increased. Moreover, we detected the miR-586 expression level in patients who had infections but did not have aGVHD, and we found that miR-586 was upregulated (P = 0.005). We also compared the plasma miR-586 level at day 7 after transplantation between aGVHD patients and control patients. In the aGVHD group, there was a considerably higher miR-586 expression in comparison with the non-aGVHD group (P < 0.05). A more significant difference between the two groups was found when the patients with infections were excluded (P = 0.004). Furthermore, receive operating characteristic (ROC) analysis indicated that a higher expression level of miR-586 at day 7 could predict impending aGVHD. The optimal cutoff value of miR-586 to predict aGVHD was 2200 copies/μL with a sensitivity of 87.5 % and specificity of 55.0 %, and the area under the curve (AUC) was 0.739 (95 % CI 0.598-0.880, P = 0.004). Our study suggests that miR-586 might participate in the occurrence of aGVHD and could be a putative target for novel aGVHD therapy. The plasma level of miR-586 at day 7 after allo-HSCT would be a potential biomarker for predicting the occurrence of aGVHD.

The Protective Role of microRNA-200c in Alzheimer's Disease Pathologies Is Induced by Beta Amyloid-Triggered Endoplasmic Reticulum Stress

“…The plasma miR-200c levels of AD patients and healthy controls were detected by TaqMan microRNA qRT-PCR assays as previously described (Wang et al, 2015). The TaqMan probe for miR-200c is 5′-FAM-CACTGGATACGACTCCATCATTACC- TAMRA-3′.…”

B-Cell-Based and Soluble Biomarkers in Body Liquids for Predicting Acute/Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

“…Circulating miRNAs have been shown to act as robust biomarkers for a various diseases, including autoimmune conditions, such as rheumatoid arthritis and systemic lupus erythematosus and tumors (91). A number of studies have also assessed the association between circulating miRNAs and the development of GvHD, with promising results (92–96). …”

“…Within Tregs, miRNA-155 targets forkhead box P3 (FoxP3), which regulates in vivo Treg survival (104). miRNA-155 also directly targets the IL-2 signaling protein suppressor of cytokine signaling 1 (SOCS1), whereby miRNA-155 deficiency in Tregs results in increased SOCS1 expression (96). This, in turn, leads to impaired activation of signal transducer and activator of transcription factor 5 (STAT5) phosphorylation and IL-2 receptor signaling (105).…”

“…More recently, Wang et al performed a study focusing on miRNA-586 expression in the plasma of HSCT patients (96). miRNA-586 was significantly upregulated in patients who developed aGvHD compared to no aGvHD as early as 7 days post-HSCT; however, expression was influenced by infection that reduced the significance of the association (96).…”

“…miRNA-586 was significantly upregulated in patients who developed aGvHD compared to no aGvHD as early as 7 days post-HSCT; however, expression was influenced by infection that reduced the significance of the association (96). As infections are common in early post-HSCT and can make distinguishing a diagnosis of aGvHD more challenging, it is important to validate the findings in larger studies as well as to elucidate the biological role of miRNA-586 in infections.…”