Accumulating evidence supports a role for exosomes in immune regulation. In this study, researchers from the Medical University of Lodz investigated the total circulating exosome transcriptome in relapsing-remitting multiple sclerosis patients (RRMS) and healthy controls (HC).
Next generation sequencing (NGS) was used to define the global RNA profile of serum exosomes in 19 RRMS patients (9 in relapse, 10 in remission) and 10 HC. The researchers analyzed 5 million reads and over 50,000 transcripts per sample, including a detailed analysis of microRNA (miRNA) differentially expressed in RRMS. The discovery set data were validated by quantification using digital quantitative PCR with an independent cohort of 63 RRMS patients (33 in relapse, 30 in remission) and 32 HC.
Flow chart of miRNA analysis in discovery and validation sets and in the PBMCculture study
Exosomal RNA NGS revealed that of 15 different classes of transcripts detected 4 circulating exosomal sequences within the miRNA category were differentially expressed in RRMS patients vs HC: hsa-miR-122-5p, hsa-miR-196b-5p, hsa-miR-301a-3p and hsa-miR-532-5p. Serum exosomal expression of these miRNA was significantly decreased during relapse in RRMS. These miRNA were also decreased in patients with a gadolinium enhancement on brain magnetic resonance imaging. In vitro secretion of these miRNA by peripheral blood mononuclear cells was also significantly impaired in RRMS.
These data show that circulating exosomes have a distinct RNA profile in RRMS. Since putative targets for these miRNA include the signal transducer and activator of transcription 3 and the cell cycle regulator aryl hydrocarbon receptor the data suggest a disturbed cell-to-cell communication in this disease. Thus exosomal miRNA might represent a useful biomarker to distinguish MS relapse.