Selected Extracellular microRNA as Potential Biomarkers of Multiple Sclerosis Activity—Preliminary Study

Abstract

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). Four distinct disease courses are known, although approximately 90 % of patients are diagnosed with the relapsing-remitting form (RRMS). The name “multiple sclerosis” pertains to the underlying pathology: the presence of demyelinating plaques in the CNS, in particular in the periventricular region, corpus callosum, cervical spine, and the cerebellum. There are ongoing efforts to discover biomarkers that would allow for an unequivocal diagnosis, assess the activity of inflammatory and neurodegenerative processes, or warn of disease progression. At present, small noncoding RNA particles-microRNA (miRNA, miR) seem to be particularly noteworthy, as they take part in posttranscriptional regulation of expression of various genes. Changes in composition as well as function of miRNA found in body fluids of MS patients are subjects of research, in the hope they prove accurate markers of MS activity. This preliminary study aims to evaluate the expression of selected extracellular microRNA particles (miRNA-let-7a, miRNA-92a, miRNA-684a) in patients experiencing MS relapse and remission, with healthy volunteers serving as a control group and to evaluate the correlation between miRNA expression and selected clinical parameters of those patients. Thirty-seven patients suffering from MS formed two examined groups: 20 patients undergoing relapse and 17 in remission. Thirty healthy volunteers formed the control group. All patients who were subjects to peripheral blood sampling had been hospitalized in the Department of Neurology and Stroke1. Four milliliters of venous whole blood had been collected into EDTA tubes. The basis for the selection of the three particular miRNA investigated in this study (miRNA-let-7a, miRNA-92a, miRNA-684a) was a preliminary bioinformatic analysis of data compiled from several medical databases, including Ovid MEDLINE®, Embase, Cochrane Database of Systematic Reviews (CDSR), miRWalk, and miRBase. The isolation of extracellular microRNA from plasma was carried out using miRNeasy Mini Kit (Qiagen) reagents. The reverse transcription was carried out with TaqMan® MicroRNA Reverse Transcription Kit (Applied Biosystems), as per manufacturers’ instructions. Standard microRNA TaqMan® tests (Applied Biosystems) were used for miRNA quantification. The qPCR were performed on a 7900 HT Fast Real-Time PCR System (Applied Biosystems) and analyzed using Sequence Detection System 2.3 software. In addition, all patients at the Department of Neurology and Stroke undergo a routine complete blood count with differential. The main objective of this study was to evaluate the expression of selected microRNA (has-miR-let-7a, miR-92a, and miR-648a) in the plasma of patients with MS during a relapse as well as in remission and attempt to correlate the acquired data with clinically relevant parameters of the disease. Finding such correlations may potentially lead to the use of miRNA as a biomarker of MS, which could help diagnose...

A plasma microRNA signature as a biomarker for acquired aplastic anemia

“…In our recent work, we identified concurrent downregulation of 4 miRNAs (miR-126-3p, miR-145-5p, miR-199a-5p, and miR-223-3p) in both CD4 + and CD8 + T cells from AA patients, 14 but dysregulation of the 4 miRNAs was not observed in AA plasma samples in the study herein. Previous reports in autoimmune diseases 12,20,[52][53][54][55][56][57][58][59] and cancers, [60][61][62][63] have also demonstrated discrepancies of expression profiles between cellular and circulating miRNAs. Systemic lupus erythematosus (SLE) patients exhibit distinct miRNA expression profiles in T cells [52][53][54][55] and plasma, 56 and miRNA profiles in T cells 12,57,58 and plasma 20,59 are inconsistent in MS.…”

Plasmatic microRNA as Potential Biomarkers of Multiple Sclerosis: Literature Review

“…Furthermore, its blood concentration should correlate with its content in the cerebrospinal fluid (CSF) [13]. Such a marker should appear in various bodily fluids shortly after the onset of the disease, and should react in response to treatment in order to be used as a prognostic tool.…”

“…Current knowledge of the biological functions of extracellular miRNA is still very limited. Early studies have indicated that cellular miRNA and extracellular miRNA found in plasma could be negatively correlated [13,19,30]. MicroR-NA seem to be universal prognostic factors.…”

Extracellular microRNAs as messengers in the central and peripheral nervous system

“…Intriguingly, while RNA molecules in the cell tend to be short-lived, circulating microRNAs show much higher stability and are protected from degradation by endogenous RNases [14]. Altered levels of specific microRNAs in body fluids have been linked to a wide range of diseases, including disorders of the nervous system [15][16][17][18][19][20][21][22][23][24][25][26][27][28]. Serum microRNA levels were altered in children with autism spectrum disorders and salivary levels have been correlated with neurodevelopmental scores [15,16].…”

“…disease [17][18][19][20], Parkinson's disease [16,21], Huntington's disease [22] and multiple sclerosis [23,24], as well as glioma [25][26][27] and stroke [28]. MicroRNA levels in the CSF were used to differentiate between glioblastoma and brain metastatic cancers [27].…”