Biomarkers For Multiple Sclerosis Diagnosis Research Articles

MicroRNAs as T Lymphocyte Regulators in Multiple Sclerosis.

MicroRNA (miRNA) is a class of endogenous non-coding small RNA with regulatory activities, which generally regulates the expression of target genes at the post-transcriptional level. Multiple Sclerosis (MS) is thought to be an autoimmune-mediated chronic inflammatory demyelinating disease of the central nervous system (CNS) that typically affect young adults. T lymphocytes play an important role in the pathogenesis of MS, and studies have suggested that miRNAs are involved in regulating the proliferation, differentiation, and functional maintenance of T lymphocytes in MS. Dysregulated expression of miRNAs may lead to the differentiation balance and dysfunction of T lymphocytes, and they are thus involved in the occurrence and development of MS. In addition, some specific miRNAs, such as miR-155 and miR-326, may have potential diagnostic values for MS or be useful for discriminating subtypes of MS. Moreover, miRNAs may be a promising therapeutic strategy for MS by regulating T lymphocyte function. By summarizing the recent literature, we reviewed the involvement of T lymphocytes in the pathogenesis of MS, the role of miRNAs in the pathogenesis and disease progression of MS by regulating T lymphocytes, the possibility of differentially expressed miRNAs to function as biomarkers for MS diagnosis, and the therapeutic potential of miRNAs in MS by regulating T lymphocytes.

Inflammation-related plasma and CSF biomarkers for multiple sclerosis

Effective biomarkers for multiple sclerosis diagnosis, assessment of prognosis, and treatment responses, in particular those measurable in blood, are largely lacking. We have investigated a broad set of protein biomarkers in cerebrospinal fluid (CSF) and plasma using a highly sensitive proteomic immunoassay. Cases from two independent cohorts were compared with healthy controls and patients with other neurological diseases. We identified and replicated 10 cerebrospinal fluid proteins including IL-12B, CD5, MIP-1a, and CXCL9 which had a combined diagnostic efficacy similar to immunoglobulin G (IgG) index and neurofilament light chain (area under the curve [AUC] = 0.95). Two plasma proteins, OSM and HGF, were also associated with multiple sclerosis in comparison to healthy controls. Sensitivity and specificity of combined CSF and plasma markers for multiple sclerosis were 85.7% and 73.5%, respectively. In the discovery cohort, eotaxin-1 (CCL11) was associated with disease duration particularly in patients who had secondary progressive disease (P CSF < 4 × 10-5, P plasma < 4 × 10-5), and plasma CCL20 was associated with disease severity (P = 4 × 10-5), although both require further validation. Treatment with natalizumab and fingolimod showed different compartmental changes in protein levels of CSF and peripheral blood, respectively, including many disease-associated markers (e.g., IL12B, CD5) showing potential application for both diagnosing disease and monitoring treatment efficacy. We report a number of multiple sclerosis biomarkers in CSF and plasma for early disease detection and potential indicators for disease activity. Of particular importance is the set of markers discovered in blood, where validated biomarkers are lacking.

LncRNAs, MALAT1 and lnc-DC as potential biomarkers for multiple sclerosis diagnosis.

Long non-coding RNAs (lncRNAs) play an important role in gene regulation and show greater tissue specificity and complexity of biological functions. There is on-going research in their contribution in autoimmune diseases like multiple sclerosis (MS). Our study aimed at the evaluation of serum levels of lncRNAs, MALAT1 and lnc-DC in MS patients and the investigation of the association between these lncRNAs and the disease activity. Serum from 45 MS patients and 45 healthy controls was separated. MALAT1 and lnc-DC expression levels were assayed by qRT-PCR. MALAT1 and lnc-DC were significantly increased in MS patients (P=0.004 and P=0.006, respectively) in comparison with controls. There was a significant increase in expression of MALAT1 in secondary progressive MS (SPMS) subgroup compared with controls (P<0.0001); however, significant elevation of lnc-DC was demonstrated in relapsing remitting MS (RRMS) subtype (P=0.003) compared with normal controls. A positive association between the expression levels of MALAT1 and lnc-DC (r = 0.513, P < 0.0001) in MS patients was detected. Moreover, positive correlation was observed between MALAT1and lnc-DC in RRMS (r = 0.569, P = 0.001). Serum levels of MALAT1 and lnc-DC may serve as potential novel molecular biomarkers for MS diagnosis and may provide a new direction for its treatment.

The mMiR-223: An inflammatory MicroRNA Involved in Pathogenesis of Multiple Sclerosis

Multiple sclerosis (MS) is the most common autoimmune inflammatory demyelinating disease that affects the brain and spinal cord. Dysregulation or mutation of miRNA genes have been linked to the pathogenesis of MS. The miRNAs are short, 20-22 nucleotide long, single-stranded regulatory and non–protein coding RNAs that modulate the expression of multiple target genes. Among miRNAs, miR-223 has been reported to play a critical role in MS. This review concentrates on the emerging role of miR-223 in inflammatory responses and specifically discusses how alterations in miR-223 expression are associated with the development of MS. This review also suggests that miR-223 can be used as a biomarker for diagnosis of MS and discovering novel therapeutics for MS treatment.

BDNF and Tau as biomarkers of severity in multiple sclerosis.

Determine if serum levels of tau and BDNF can be used as severity biomarkers in multiple sclerosis (MS). Subjects with MS, older than 18 and younger than 55years old were included; 74 patients with a diagnosis of relapsing-remitting MS, 11 with secondary-progressive MS, and 88 controls were included. Total tau and BDNF were measured by Western blot. Increased tau and decreased BDNF in MS patients compared with controls was found. Total-tau has a peak in relapsing-remitting MS, the second decile of the multiple sclerosis severity score, and in the lowest expanded disability status scale and is no different than controls for secondary-progressive MS patients and the most severe cases of MS. BDNF is a good biomarker for diagnosis of MS but not for severity or progression. Tau appears to have a more active role in the progression of MS.