Myasthenia gravis (MG) is an autoantibody-mediated postsynaptic neuromuscular junction disorder. Anti-acetylcholine receptor antibodies are found in about 80% of patients with MG [1], and numerous auto-antibodies have been recently discovered; muscle-specific tyrosine kinase (MuSK) [2], low-density lipoprotein receptor-related protein 4 (LRP4) [3], agrin [4], voltage-gated K+ channel Kv1.4 [5], ryanodine receptor [6] and cortactin [7]. Chronic immunosuppressive treatment (ISTX), such as tacrolimus, azathioprine, mycophenolate mofetil and prednisolone, is required in most patients at some point in their courses, in order to maintain disease stability. Nevertheless, appropriate biomarkers that reflect disease activity or toxicity of ISTX lack [8]. Herein, we immunophenotyped peripheral blood mononuclear cells (PBMC) from participants and tested if B cell subsets were altered by disease activity or ISTX. Furthermore, given that MG is an apparently antibody-specific autoimmune disease, we analyzed transcriptional profiles of memory B cells (CD19+ CD27+) in order to develop appropriate biomarkers to monitor disease status. For transcriptome study, we used Nanostring analysis which is a digital multiplexed mRNA assay that provides highly reproducible data even in small-sized samples, by detecting native RNAs directly, without reverse transcription or amplification [9]. MATERIALS AND METHODS Study subjects A total of 21 patients with MG and 10 healthy controls were recruited from December 2015 to August 2019 in Seoul Metropolitan Government Boramae Medical Center. Written informed consent was obtained from all participants. This study was approved by the local institutional review board (IRB no. 20151016/16-2015-147/111).

Dysregulation of microRNAs (miRNA) in small extracellular vesicles (sEV) such as exosomes have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Although circulating cell-free miRNA have been extensively investigated in ALS, sEV-derived miRNAs have not been systemically explored yet. Here, we performed small RNA sequencing analysis of serum sEV and identified 5 differentially expressed miRNA in a discovery cohort of 12 patients and 11 age- and sex-matched healthy controls (fold change > 2, p < 0.05). Two of them (up- and down-regulation of miR-23c and miR192-5p, respectively) were confirmed in a separate validation cohort (18 patients and 15 healthy controls) by droplet digital PCR. Bioinformatic analysis revealed that these two miRNAs interact with distinct sets of target genes and involve biological processes relevant to the pathomechanism of ALS. Our results suggest that circulating sEV from ALS patients have distinct miRNA profiles which may be potentially useful as a biomarker of the disease.