025 – Circulating miR-191-5p, miR-223-3p, miR-24-3p and miR-128-3p in sera of MS patients, longitudinal study
Julia Vistbakka (1) – Emma Raitoharju (1) – Irina Elovaara (1) – Terho Lehtimki (1) – Marja-Liisa Sumelahti (1) – Sanna Hagman (1)
Tampere University, Medicine and Life Sciences, Tampere, Finland (1)
Background: Biomarkers that could be used in early diagnosis of multiple sclerosis (MS), segregation of disease subtypes and discrimination of the aggressive disease course from the benign one are urgently needed. Aberrant miRNA expression levels were previously reported in multiple MS studies, with less attention paid to circulating miRNAs, especially to their longitudinal stability.
Objective: Assess the stability of specific miRNA expression in longitudinal study to highlight its promising biomarker potential. Study their association to disability accumulation and disease activity over the 4-year follow-up cohort, as well as to evaluate their correlations to MRI findings.
Methods: We analyzed four miRNAs (miR-24-3p, miR-191-5p, miR-128-3p and miR-223-3p), that we previously found to be potentially associated with MS. Their expression levels were analyzed in sera samples of 18 patients with clinically isolated syndrome (CIS) and 57 patients with clinically defined MS (CDMS), including 28 relapsing-remitting (RRMS), 14 secondary progressive (SPMS) and 15 primary progressive (PPMS), at the baseline, 2 and 4-years after the study enrollment, as well as in 32 age and sex matched healthy controls (HC). All the patients underwent MRI examination during the follow-up.
Results: On the baseline, miR-191-5p was overexpressed in CDMS and RRMS, while miR-128-3p was overexpressed in CDMS and PPMS, as compared to HCs. No differences in comparison to CIS or between the MS subtypes were observed. All four miRNAs showed longitudinal variability of various degree in all the MS subgroups (miR-191-5p and miR-223-3p) or only in PPMS (miR-24-3p, miR-128-3p). No longitudinal variability was detected in the CIS. In addition, miR-223-3p negatively correlated with T1 volumes in SPMS and PPMS and with the progression index in PPMS. While, miR-191-5p positively correlated with age, the progression index and EDSS in RRMS and with age and disease duration in SPMS. In turn, miR-128-3p positively correlated with age, progression index and EDSS in RRMS.
Conclusion: Our results indicate an abnormal expression and longitudinal variability of selected microRNAs in MS, which appears to be linked to the MS events.