Differences in gene expression patterns have been documented not only in Multiple Sclerosis patients versus healthy controls but also in the relapse of the disease. Recently a new gene expression modulator has been identified: the microRNA or miRNA. The aim of this work is to analyze the possible role of miRNAs in multiple sclerosis, focusing on the relapse stage. We have analyzed the expression patterns of 364 miRNAs in PBMC obtained from multiple sclerosis patients in relapse status, in remission status and healthy controls. The expression patterns of the miRNAs with significantly different expression were validated in an independent set of samples. In order to determine the effect of the miRNAs, the expression of some predicted target genes of these were studied by qPCR. Gene interaction networks were constructed in order to obtain a co-expression and multivariate view of the experimental data. The data analysis and later validation reveal that two miRNAs (hsa-miR-18b and hsa-miR-599) may be relevant at the time of relapse and that another miRNA (hsa-miR-96) may be involved in remission. The genes targeted by hsa-miR-96 are involved in immunological pathways as Interleukin signaling and in other pathways as wnt signaling. This work highlights the importance of miRNA expression in the molecular mechanisms implicated in the disease. Moreover, the proposed involvement of these small molecules in multiple sclerosis opens up a new therapeutic approach to explore and highlight some candidate biomarker targets in MS.

We suggest that MPs play a role in MS pathogenesis, reflecting disease status with an increment of their shedding during inflammatory periods and turning to baseline during chronic progressive degeneration.

Objective:To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort.Methods:Using data from the MSBase Registry, we included pregnancies conceived after 31 Dec 2010 from women with relapsing-remitting MS or clinically isolated syndrome. Predictors of intrapartum relapse, and postpartum relapse and disability progression were determined by clustered logistic regression or Cox regression analyses.Results:We included 1998 pregnancies from 1619 women with MS. Preconception annualized relapse rate (ARR) was 0.29 (95% CI 0.27-0.32), fell to 0.19 (0.14-0.24) in third trimester, and increased to 0.59 (0.51-0.67) in early postpartum. Among women who used fingolimod or natalizumab, ARR before pregnancy was 0.37 (0.28-0.49) and 0.29 (0.22-0.37), respectively, and increased during pregnancy. Intrapartum ARR decreased with preconception dimethyl fumarate use. ARR spiked after delivery across all DMT groups. Natalizumab continuation into pregnancy reduced the odds of relapse during pregnancy (OR 0.76 per month [0.60-0.95], p=0.017). DMT re-initiation with natalizumab protected against postpartum relapse (HR 0.11 [0.04-0.32], p<0.0001). Breastfeeding women were less likely to relapse (HR 0.61 [0.41-0.91], p=0.016). 5.6% of pregnancies were followed by confirmed disability progression, predicted by higher relapse activity in pregnancy and postpartum.Conclusion:Intrapartum and postpartum relapse probabilities increased among women with MS after natalizumab or fingolimod cessation. In women considered to be at high relapse risk, use of natalizumab before pregnancy and continued up to 34 weeks gestation, with early re-initiation after delivery is an effective option to minimize relapse risks. Strategies of DMT use have to be balanced against potential fetal/neonatal complications.

Background: Multiple sclerosis (MS) onset before puberty may have a distinct clinical presenta-