Radiologically Isolated Syndrome: Targeting miRNAs as Prognostic Biomarkers

Abstract

Aim: Some clinical and biological characteristics have been described as prognostic factors for clinical conversion into clinically definite multiple sclerosis in radiologically isolated syndrome (RIS) population. The aim of this study was to assess signatures of circulating miRNAs in those patients according to their conversion status after 5 years of follow-up. Patients & methods: OpenArray plates assessing 216 miRNA candidates were run in 15 RIS patients, and their relative abundances were analyzed. Results: A specific profile of deregulated circulating miRNAs (miR-144-3p, miR-448 and miR-653-3p in cerebrospinal fluid and miR-142-3p, miR-338-3p, miR-363-3p, miR-374b-5p, miR-424-5p, miR-483-3p in plasma) differentiated individuals who remained as RIS after 5 years of follow-up. Conclusion: Circulating miRNAs might be used as prognostic biomarkers for RIS patients.

Identification of Novel Key Genes and Pathways in Multiple Sclerosis Based on Weighted Gene Coexpression Network Analysis and Long Noncoding RNA-Associated Competing Endogenous RNA Network

“…The level of the gene with the highest node degree, miR-17-5p, has been demonstrated to be increased in CD4 (+) cells from patients with MS, implying the reliability of the current analysis [41]. Moreover, circulating miR-338-3p has been nominated as a potential MS diagnostic biomarker for patients with radiologically isolated syndrome [42]. Despite the lack of evidence concerning the role of lncRNAs in MS, these noncoding RNAs have been implicated in numerous disease contexts.…”

Biological Markers in Early Multiple Sclerosis: the Paved Way for Radiologically Isolated Syndrome

“…Lower 25(OH)D levels were associated with the risk of clinical events in a large cohort of CIS patients in univariate analysis, but EBNA1-IgG and smoking status as defined by cotinine levels (>14 ng/ml) were not ( 25 ). In a small RIS cohort, there was no difference in 25(OH)D levels in the serum of converters or non-converters ( 20 ). The predictive value of 25(OH)D deficiency should be investigated further, as the relatively minor clinical impact of vitamin D therapy in MS may be enhanced if started before disease onset ( 26 , 27 ).…”

“…In RIS, the presence of OCBs is predictive of clinical conversion in adults ( 33 ) and children ( 34 , 35 ) ( Table 1 ), although the presence of OCBs is not correlated with the conversion time in adults ( 33 ). Conversely, the IgG index has not shown an independent prognostic value ( 8 , 20 ). In large cohorts, abnormal CSF, defined as the presence of ≥2 OCBs and/or an IgG index >0.7, revealed a relevant predictive value for disease activity ( 5 , 6 , 8 ).…”

“…Indeed, cCHI3L1may reflect non-lymphocytic low-grade inflammation leading to active neurodegeneration ( 79 ), explaining its association with neurological disability quantified by EDSS in PPMS ( 80 ). However, all studies consistently show the absence of prognostic value of cCHI3L1 in RIS ( 20 , 33 , 36 ), suggesting that astrocytic and microglial activation is too scarce at the pre-symptomatic stage of MS. However, chitotriosidase and chitinase 3-like protein 2 (CHI3L2), two other members of the chitin family with similar properties, also need to be evaluated ( 75 , 81 , 82 ).…”

“…HLA-DRB1∗1501 is the main allele responsible for the genetic risk of MS in patients with European ancestry ( 18 ). It has also been associated with the risk of clinical events in CIS patients ( 19 ), but not in RIS patients ( 20 ). Although they are not routinely determined in MS and RIS, analysis of genetic variants associated with MS might still have a minor interest in clinical care.…”