ECTRIMS eLearning

Serum levels of mir-128-3p are associated to clinical course and disease activity in multiple sclerosis
Author(s): ,
M. Zanoni
Affiliations:
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona - Neurology Section
,
M.M. Gomez-Lira
Affiliations:
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona - Biology and Genetics Section, Verona, Italy
,
E. Orlandi
Affiliations:
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona - Biology and Genetics Section, Verona, Italy
,
M. Bongianni
Affiliations:
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona - Neurology Section
,
M. Turatti
Affiliations:
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona - Neurology Section
,
A. Marangi
Affiliations:
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona - Neurology Section
,
F. Gobbin
Affiliations:
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona - Neurology Section
,
M. Calabrese
Affiliations:
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona - Neurology Section
,
S. Monaco
Affiliations:
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona - Neurology Section
,
M.D. Benedetti
Affiliations:
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona - Neurology Section
A. Gajofatto
Affiliations:
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona - Neurology Section
ECTRIMS Learn. Zanoni M. 10/10/18; 229392; EP1555
Mattia Zanoni
Mattia Zanoni
Contributions
Abstract

Abstract: EP1555

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Biomarkers

Background: MicroRNAs (miRs) are gene transcription regulators, which have emerged as novel candidate biomarkers for multiple sclerosis (MS). The main goal of the study was to investigate the association between miRs expression in serum of patients with MS and the disease course.
Methods: Serum sample of consecutive patients with clinically isolated syndrome (CIS) or MS stored at Verona Laboratory of Neuropathology were analysed. All cases were followed clinically at Verona MS Centre and had a brain MRI performed by a standardized protocol at time of serum collection. Serum samples from subjects with other neurological conditions were used as controls. Based on earlier studies, a panel of ten circulating candidate miRs extracted from serum were analysed by Real-Time PCR. miR-425-5p, which showed the most stable expression across samples in a preliminary screening, was used as normalizer. Non-parametric statistical tests were used to analyse the association between miRs expression and outcomes of interest, including relapse occurrence and expanded disability status scale (EDSS) score change over time.
Results: Serum samples from 72 CIS/MS cases and 17 controls were analysed. Mean age at sample collection was 37 ±12 years. Among cases, 59 had a relapsing course, including 10 CIS patients, and 13 had a progressive disease. Mean follow-up duration was 16 months. No significant differences were found in miRs levels between cases and controls and according to gender, age, and presence of contrast-enhancing lesions on MRI. We found a significant decrease of miR-128-3p levels in patients who had one or more relapses on follow-up compared to cases with no relapses (median ratio 0.82 vs. 1.64; p=0.014); also, there was a significant inverse correlation between miR-128-3p levels and relapse rate (r= -0.44, p=0.008). In addition, miR-128-3p levels were significantly higher in patients with progressive compared to relapsing MS (2.86 vs 0.73, p=0.009). We observed a significant correlation between miR-223-5p levels and EDSS score at 1 year after sample collection (r=0.41, p=0.032). Finally, miR-92a-5p levels were significantly higher in patients with EDSS score increase compared to stable patients (0.1 vs 0, p=0.02).
Conclusions: This study highlights the existing connections between the expression of miRs involved in regulatory mechanisms of the immune system and MS clinical course. In particular, serum levels of mir-128-3p seem to be related to disease activity and progression.
Disclosure: Dr. Zanoni: nothing to disclose; Dr. Gomez-Lira: nothing to disclose; Dr. Orlandi: nothing to disclose; Dr. Bongianni: nothing to disclose; Dr. Turatti: nothing to disclose; Dr. Marangi: nothing to disclose; Dr. Gobbin: nothing to disclose; Dr. Monaco: nothing to disclose; Dr. Benedetti: nothing to disclose; Dr. Calabrese received payment for development of educational presentations including service on speakers bureaus by BiogenElan, Genzyme, TEVA, BayerSchering, he received travel/accomodation expenses by Novartis Pharma, Genzyme, Biogen idec, Merck Serono, BayerSchering, TEVA, and Advisory Board membership by BayerShering,Genzyme, Biogen Idec; Dr. Gajofatto received speaker honoraria from Merck.
The study was supported by Cariverona Foundation and Merck.

Abstract: EP1555

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Biomarkers

Background: MicroRNAs (miRs) are gene transcription regulators, which have emerged as novel candidate biomarkers for multiple sclerosis (MS). The main goal of the study was to investigate the association between miRs expression in serum of patients with MS and the disease course.
Methods: Serum sample of consecutive patients with clinically isolated syndrome (CIS) or MS stored at Verona Laboratory of Neuropathology were analysed. All cases were followed clinically at Verona MS Centre and had a brain MRI performed by a standardized protocol at time of serum collection. Serum samples from subjects with other neurological conditions were used as controls. Based on earlier studies, a panel of ten circulating candidate miRs extracted from serum were analysed by Real-Time PCR. miR-425-5p, which showed the most stable expression across samples in a preliminary screening, was used as normalizer. Non-parametric statistical tests were used to analyse the association between miRs expression and outcomes of interest, including relapse occurrence and expanded disability status scale (EDSS) score change over time.
Results: Serum samples from 72 CIS/MS cases and 17 controls were analysed. Mean age at sample collection was 37 ±12 years. Among cases, 59 had a relapsing course, including 10 CIS patients, and 13 had a progressive disease. Mean follow-up duration was 16 months. No significant differences were found in miRs levels between cases and controls and according to gender, age, and presence of contrast-enhancing lesions on MRI. We found a significant decrease of miR-128-3p levels in patients who had one or more relapses on follow-up compared to cases with no relapses (median ratio 0.82 vs. 1.64; p=0.014); also, there was a significant inverse correlation between miR-128-3p levels and relapse rate (r= -0.44, p=0.008). In addition, miR-128-3p levels were significantly higher in patients with progressive compared to relapsing MS (2.86 vs 0.73, p=0.009). We observed a significant correlation between miR-223-5p levels and EDSS score at 1 year after sample collection (r=0.41, p=0.032). Finally, miR-92a-5p levels were significantly higher in patients with EDSS score increase compared to stable patients (0.1 vs 0, p=0.02).
Conclusions: This study highlights the existing connections between the expression of miRs involved in regulatory mechanisms of the immune system and MS clinical course. In particular, serum levels of mir-128-3p seem to be related to disease activity and progression.
Disclosure: Dr. Zanoni: nothing to disclose; Dr. Gomez-Lira: nothing to disclose; Dr. Orlandi: nothing to disclose; Dr. Bongianni: nothing to disclose; Dr. Turatti: nothing to disclose; Dr. Marangi: nothing to disclose; Dr. Gobbin: nothing to disclose; Dr. Monaco: nothing to disclose; Dr. Benedetti: nothing to disclose; Dr. Calabrese received payment for development of educational presentations including service on speakers bureaus by BiogenElan, Genzyme, TEVA, BayerSchering, he received travel/accomodation expenses by Novartis Pharma, Genzyme, Biogen idec, Merck Serono, BayerSchering, TEVA, and Advisory Board membership by BayerShering,Genzyme, Biogen Idec; Dr. Gajofatto received speaker honoraria from Merck.
The study was supported by Cariverona Foundation and Merck.

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