Plasma Exosomal MiR-106a-5p:A New Potential Biomarker For Myasthenia Gravis

Objective: Detecting different expression of plasma exosomal miRNAs between patients with myasthenia gravis(MG)and healthy controls to explore the potential diagnostic value of plasma exosomal miRNAs in MG.Methods: Consecutive patients with OMG(Ocular Myasthenia Gravis)or GMG(Generalized Myasthenia Gravis)visited neurology clinic or admitted to the Department of Neurology,the First Affiliated Hospital of Guangxi Medical University between March 2017 and October 2018 were enrolled in the study.MG diagnoses were based on the observation of fatigable weakness and at least one of the following: a positive AchR-Ab or intra-muscular neostigmine test result,or a > 10% decrement result during 2-Hz repetitive nerve stimulation.MG severity was assessed via quantitative MG scores(QMGS).plasma exosomal miRNAs from 8 patients with MG(OGM:n=4;GMG:n=4)and 2healthy controls(HCs)were sequenced to screen differentially expressed miRNAs.Plasma samples from 92 patients with MG and 49 age-matched HCs were screened via qRT-PCR for differentially expressed exosomal miRNAs.A Spearman’s correlation analysis was used to assess correlations between candidate miRNAs and patient quantitative MG scores(QMGS).An area underthe curve(AUC)of the receiver operating characteristic(ROC)curve analysis was used to evaluate the diagnostic accuracy of the identified miRNAs for MG.The biological functions of the altered levels of miRNAs and their target genes were predicted using bioinformatics.Results: The relative expression of Plasma exosomal miR-106a-5p was significantly different among ocular myasthenia gravis(OMG):1.30(1.64)/generalized myasthenia gravis(GMG)patients:0.66(0.98)and HCs:1.72(1.63)by Kruskal-Wallis test(H=25.268,P=0.000).Plasma exosomal miR-106a-5p levels were significantly decreased in patients with MG compared to HCs and were decreased in GMG patients than in OMG patients.And moreover,miR-106a-5p was shown to be associated with patient QMGS.The AUC values calculated for hsa-miR-106a-5p were found to be 0.728 and 0.813 in patients with Ocular and Generalized MG,respectively,compared to HCs.Bioinformatics analysis suggested that its target genes were involved in biological pathways associated with myasthenia gravis.CONCLUSION: Exosomal miR-106a-5p is a promising potential biomarker for MG.