Circulating miRNAs in myasthenia gravis: miR‐150‐5p as a new potential biomarker

Abstract

ObjectiveMyasthenia gravis (MG) is a chronic autoimmune disorder where autoantibodies target the nicotinic acetylcholine receptors (AChR+) in about 85% of cases, in which the thymus is considered to play a pathogenic role. As there are no reliable biomarkers to monitor disease status in MG, we analyzed circulating miRNAs in sera of MG patients to find disease-specific miRNAs.MethodsOverall, 168 miRNAs were analyzed in serum samples from four AChR+ MG patients and four healthy controls using Exiqon Focus miRNA polymerase chain reaction (PCR) Panel I + II. Specific accumulation pattern of 13 miRNAs from the discovery set was subsequently investigated in the sera of 16 AChR+ MG patients and 16 healthy controls. All patients were without immunosuppressive treatment. Selected specific miRNAs were further analyzed in the serum of nine MG patients before and after thymectomy to assess the effect of thymus removal on the accumulation of the candidate miRNAs in patient sera.ResultsThree miRNAs were specifically dysregulated in AChR+ MG patient sera samples. Hsa-miR150-5p, which induces T-cell differentiation, as well as hsa-miR21-5p, a regulator of Th1 versus Th2 cell responses, were specifically elevated in MG sera. Additionally, hsa-miR27a-3p, involved in natural killer (NK) cell cytotoxicity, was decreased in MG. Hsa-miR150-5p levels had the highest association with MG and were significantly reduced after thymus removal in correlation with disease improvement.InterpretationWe propose that the validated miRNAs: hsa-miR150-5p, hsa-miR21-5p, and hsa-miR27a-3p can serve as novel serum biomarkers in AChR+ MG. Hsa-miR-150-5p could be a helpful marker to monitor disease severity.

A plasma microRNA signature as a biomarker for acquired aplastic anemia

“…Of note, regardless of discrepancies between cellular and circulating miRNA profiles, we could observe some common miRNA signatures in both AA and MG, such as decreased miR-145-5p in T cells 14,64 and increased miR-150-5p in plasma specimens. 21 In conclusion, we demonstrate that expression levels of 3 dysregulated miRNAs in AA plasma associate with clinical parameters and normalize after IST, suggesting their use as potential biomarkers in AA. Importantly, we developed a diagnostic logistic model using combined miRNA panels for diagnosis.…”

“…28 MiR-150-5p is a circulating biomarker in female MG patients without immunosuppressive drug treatment, as the miR-150-5p level is reduced with clinical improvement after Circulating microRNA profile in aplastic anemia haematologica | 2017; 102 (1) 75 thymectomy. 21 Why miRNA expression changes is unknown. MiRNAs are released into the circulation as a result of apoptotic and necrotic cell death.…”

“…[17][18][19][20][21] Challenges in the analysis of circulating miRNAs include pre-analytical decisions (such as sample storage and processing) and post-analytical assessments (data normalization). 17 Detailed analyses of miRNA spectra in serum and plasma recommend plasma over serum to reduce sample-to-sample variations induced by serum coagulation, 26 and we used EDTA anticoagulated plasma in this study to avoid such variations.…”

“…18,19 Recent studies have also identified circulating miRNAs as biomarkers to monitor the disease state in T cell-mediated autoimmune diseases, such as MS and myasthenia gravis (MG). 20,21 However, miRNAs have yet to be explored in the serum or plasma of AA. The purpose of our study was to analyze the circulating miRNA profile in the plasma of AA patients and to assess whether specific miRNAs could serve as new biomarkers for AA.…”

Identification of microRNAs and their target genes in Alport syndrome using deep sequencing of iPSCs samples

“…However, other differentially expressed miRNAs are also involved in genetic diseases. For example, hsa-miR-150-5p probably could serve as a novel serum biomarker in myasthenia gravis as well as in the prediction of disease severity (Punga et al, 2014). Due to the importance of miRNA in mediating the translation of target miRNA into protein, hsa-miR-1228-5p could be used to differentiate hepatocellular carcinoma patients from healthy subjects and cirrhosis patients (Tan et al, 2014).…”