Abstract
Background: Erythrocytes may be involved in MS through impaired antioxidant capacity and haemorheological modifications. Erythrocytes harbour microRNAs, which may silence translation. Some microRNAs are transcribed as clusters, exerting increased control over the same pathway. Erythrocyte microRNAs may participate in intercellular communication through extracellular vesicles (EVs).
Objective: To identify erythrocyte microRNAs’ diagnostic and disease activity biomarker potential and determine their possible role as a form of intercellular communication in MS through extracellular vesicles.
Methods: Erythrocyte microRNAs were sequenced from 11 relapsing-remitting MS (RRMS), 12 secondary progressive MS (SPMS), and 22 healthy controls (HCs). Differentially expressed microRNAs were further assessed with a targeted assay in an independent cohort [21 RRMS - remission, 14 RRMS - relapse, 11 SPMS, 25 HCs, 20 migraine patients (MPs)]. Correlations between microRNAs and EDSS, MSSS, ARMSS, and cognitive screens were assessed. Plasma extracellular vesicles were surveyed by flow cytometry.
Results: During relapse miR-183-5p and miR-182-5p, miR-183 cluster members, showed increased expression compared to remission (3.15-fold, p<0.001; 2.44-fold, p<0.001), SPMS, HCs, and MPs. This expression correlated with physical disability. The third miR-183 cluster member, miR-96-5p, correlated with cognitive disability. MiR-183 cluster target genes are enriched in pathways related to transendothelial migration and immune cell activation. Erythrocyte-derived EVs, which may carry microRNAs to recipient cells, were also increased in MS.
Conclusions: Erythrocyte miR-183 cluster expression was increased during relapse, correlated with MS severity, and may serve as an activity marker. Increased expression appeared to be MS specific. Erythrocyte miR-183 cluster microRNAs might be involved in intercellular communication through EVs, which were upregulated in MS.
Objective: To identify erythrocyte microRNAs’ diagnostic and disease activity biomarker potential and determine their possible role as a form of intercellular communication in MS through extracellular vesicles.
Methods: Erythrocyte microRNAs were sequenced from 11 relapsing-remitting MS (RRMS), 12 secondary progressive MS (SPMS), and 22 healthy controls (HCs). Differentially expressed microRNAs were further assessed with a targeted assay in an independent cohort [21 RRMS - remission, 14 RRMS - relapse, 11 SPMS, 25 HCs, 20 migraine patients (MPs)]. Correlations between microRNAs and EDSS, MSSS, ARMSS, and cognitive screens were assessed. Plasma extracellular vesicles were surveyed by flow cytometry.
Results: During relapse miR-183-5p and miR-182-5p, miR-183 cluster members, showed increased expression compared to remission (3.15-fold, p<0.001; 2.44-fold, p<0.001), SPMS, HCs, and MPs. This expression correlated with physical disability. The third miR-183 cluster member, miR-96-5p, correlated with cognitive disability. MiR-183 cluster target genes are enriched in pathways related to transendothelial migration and immune cell activation. Erythrocyte-derived EVs, which may carry microRNAs to recipient cells, were also increased in MS.
Conclusions: Erythrocyte miR-183 cluster expression was increased during relapse, correlated with MS severity, and may serve as an activity marker. Increased expression appeared to be MS specific. Erythrocyte miR-183 cluster microRNAs might be involved in intercellular communication through EVs, which were upregulated in MS.
| Original language | English |
|---|---|
| Pages (from-to) | NP27 |
| Number of pages | 1 |
| Journal | Multiple Sclerosis Journal |
| Volume | 26 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2020 |
| Event | Conference of MS-Research-Australia - Melbourne, Australia Duration: 31 Oct 2019 → 1 Nov 2019 |