MicroRNA serum profiles and chronic graft-versus-host disease

Abstract

Chronic graft versus host disease (cGVHD) is the most common long-term complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). During the last decade, the interest of micro RNAs (miRNAs) in the pathophysiological process of cGVHD has increased. The objectives of this study were to investigate a wide range of serum miRNAs in allografted patients and identify associations between miRNAs and cGVHD. The study included 79 allotransplanted adults, where serum samples were obtained one year after the allo-HSCT, and miRNA profiling analysis in serum was performed. 50 of the 79 patients (63%) had signs of cGVHD at the one-year post-allo-HSCT control. miRNA-sequencing analysis revealed 1380 different miRNAs detected for at least one patient, while 233 miRNAs (17%) were detected in more than 70 patients. We identified ten miRNAs that differed significantly between patients with and without cGVHD (p <0.005, false discovery rate (FDR) <0.1), and all or these miRNAs were detected for >75 of the patients. Furthermore, five distinct miRNAs; miR-365-3p, miR-148-3p, miR-122-5p, miR-378-3p, and miR-192-5p, were found to be particularly associated with cGVHD in our analysis and validated by receiver operating characteristics (ROC) analysis. Based on only three miRNAs, miR-365-3p, miR-148-3p, and miR-378-3p, we developed a miRNA signature which by bioinformatic approaches and linear regression model utterly improved our potential diagnostic biomarker model for cGVHD. We conclude that miRNAs are differently expressed among patients with and without cGVHD, although further and larger studies are needed to validate our present findings.

Musculoskeletal Chronic Graft versus Host Disease—A Rare Complication to Allogeneic Hematopoietic Stem Cell Transplant: A Case-Based Report and Review of the Literature

“…General markers of inflammation such as CRP and ferritin could be used, although would in general reflect unspecified inflammatory conditions [ 44 , 45 ]. New biomarkers are entering the research fields of cGVHD [ 46 , 47 ], although if they have a diagnostic or prognostic impact in musculoskeletal cGVHD remains unanswered.…”

Role of microRNAs in Immune Regulation with Translational and Clinical Applications

“…According to a murine model of acute GVHD, the infusion of miR-223 agomiR resulted in symptom relief and decreased production of inflammatory cytokines [210]. Chronic GVHD has been associated with the dysregulated expression of miR-122-5p, miR-148-3p, miR-192-5p, miR-365-3p and miR-378-3p [211,212].…”

Differential expression of miRNA-769-5p and Smad2 in patients with or without oral cGVHD

“…Recent studies have shed light on the role of microRNAs (miRNAs) in cGVHD pathogenesis. 12 Reikvam et al were the first to report miRNA serum profiles in cGVHD, 13 and miRNA profiles from plasma extracellular vesicles (EVs) have been considered markers of cGVHD onset. 14 However, owing to the distinct microenvironments of various organs and tissues, the miRNAs associated with the disease also exhibit variations.…”