Background

MicroRNAs (miRNAs) are endogenous, non coding, small RNAs with post-transcriptional regulating functions. They participate in several cellular processes, including inflammation, neurodegeneration and remyelination

Objectives

To correlate serum miRNAs profile expression with disability, cognitive functioning and brain volume in patients with remitting-relapsing multiple sclerosis (RRMS)

Methods

Cross-sectional study in RRMS patients on stable treatment with glatiramer acetate (GA) during at least 6 months.

We selected the 20 best miRNAs candidates for RRMS and cognitive dysfunction through simple topological analysis (Anaxomics ®). MiRNAs profile was determined with LNA-based PCR (Exiqon). Clinical variables were Expanded Disability Status Scale (EDSS), Symbol Digit Modalities Test (SDMT) and brain volume (whole brain volume, grey matter volume, white matter volume, cerebellum volume, basal ganglia volume and T1 lesion load volume) (automatic software NeuroQuant ®). Correlation was analyzed with Spearman correlation coefficient (r) (p<0,05; software: SPSS)

Results

We included 20 patients (13 women), age 38,2 (29,4, 47,8) years, duration of disease: 5,1 (1,5, 8,5) years, and time on GA 2,1 (0,8, 6) years. We found a pathogenic association between miR.146a.5p and has.mir.9.5p with EDSS (r:0,434, p=0,03; r:0,516, p=0,028); miR.146a.5p with SDMT (r:-0,476, p=0,016); has.mir.9.5p with thalamus (r:-0,545, p=0,036), and miR.200c.3p with pallidum and cerebellum (r:-0,675, p=0,002; r:-0,472, p=0,048).

Conclusions

MiRNAs could be useful biomarkers in multiple sclerosis. We would like to highlight the association of proinflammatory has.mir.9.5p with EDSS and thalamus volume. They are needed more studies to confirm this findings.

Background

Viruses have been involved in multiple sclerosis (MS) in last years. However, almost all of the studies published so far have focused on patients with relapsing-remitting MS (RRMS), with no data about viruses in patients with progressive primary MS (PPMS). Due to the differences that exist between these two forms of MS it would be interesting to know if there is also differences regarding viruses previously related to the etiopathogenesis of the disease.

Objectives

The aim of this study was to analyze the prevalence and titters of different viral antibodies: IgG against EBNA-1 and VCA of Epstein-Barr virus (EBV), IgG and IgM against Human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV), in PPMS patients and to compare those results with other cohort of RRMS patients.

Methods

A total of 166 MS patients were recruited: 71 with PPMS and 95 with RRMS (mean age: 48 and 43.6 years, respectively; gender: 47.9% and 61% female, respectively). We analyzed the presence and titters of the antibodies above mentioned with ELISA commercial kits, following manufacturer instructions.

Results

1. Herpesvirus prevalences: we only found a statistical significant difference for IgG antibodies against EBNA-1 of EBV (84.5% of PPMS patients were positive vs. 97.8% of RRMS patients; p=0.002). When we analyzed these prevalences by age groups (<45 and >45 years), we only found statistical significant differences between PPMS and RRMS patients under 45 years: 84.6% of PPMS patients were positive for IgG against EBNA-1 vs. 100% of RRMS patients (p=0.015), and 26.9% of PPMS patients were positive for IgM against HHV-6 vs. 7.7% of RRMS patients (p=0.021). 2. Herpesvirus titters: we found that IgG titters against CMV were higher among PPMS patients than in RRMS patients (31.3 AU vs. 16.01 AU, p=0.0001); IgG titters against HHV-6 were also higher in PPMS patients (29.3 AU vs. 20.5, p=0.004); IgG titters against EBNA-1 of EBV were lower in PPMS patients than in RRMS patients (16.4 AU vs. 22.8 AU, p<0.0001).

Conclusions

We have found statistical significant differences between different herpesvirus prevalences and titters between PPMS and RRMS patients that should be deeper studied to evaluate their possible contribution to the existing differences between these two forms of MS.

Background

MicroRNAs (miRNAs) are endogenous, non coding, small RNAs with post-transcriptional regulating functions. They participate in several cellular processes, including inflammation, neurodegeneration and remyelination

Objectives

To correlate serum miRNAs profile expression with disability, cognitive functioning and brain volume in patients with remitting-relapsing multiple sclerosis (RRMS)

Methods

Cross-sectional study in RRMS patients on stable treatment with glatiramer acetate (GA) during at least 6 months.

We selected the 20 best miRNAs candidates for RRMS and cognitive dysfunction through simple topological analysis (Anaxomics ®). MiRNAs profile was determined with LNA-based PCR (Exiqon). Clinical variables were Expanded Disability Status Scale (EDSS), Symbol Digit Modalities Test (SDMT) and brain volume (whole brain volume, grey matter volume, white matter volume, cerebellum volume, basal ganglia volume and T1 lesion load volume) (automatic software NeuroQuant ®). Correlation was analyzed with Spearman correlation coefficient (r) (p<0,05; software: SPSS)

Results

We included 20 patients (13 women), age 38,2 (29,4, 47,8) years, duration of disease: 5,1 (1,5, 8,5) years, and time on GA 2,1 (0,8, 6) years. We found a pathogenic association between miR.146a.5p and has.mir.9.5p with EDSS (r:0,434, p=0,03; r:0,516, p=0,028); miR.146a.5p with SDMT (r:-0,476, p=0,016); has.mir.9.5p with thalamus (r:-0,545, p=0,036), and miR.200c.3p with pallidum and cerebellum (r:-0,675, p=0,002; r:-0,472, p=0,048).

Conclusions

MiRNAs could be useful biomarkers in multiple sclerosis. We would like to highlight the association of proinflammatory has.mir.9.5p with EDSS and thalamus volume. They are needed more studies to confirm this findings.