Serum Of Relapsing-remitting Multiple Sclerosis Patients Research Articles

Multiplex Analysis of Cerebrospinal Fluid and Serum Exosomes MicroRNAs of Untreated Relapsing Remitting Multiple Sclerosis (RRMS) and Proposing Noninvasive Diagnostic Biomarkers.

Exosomal microRNAs (miRNAs) are emerging diagnostic biomarkers for neurodegenerative diseases. In this study, we aimed to detect relapsing-remitting multiple sclerosis (RRMS)-specific miRNAs in cerebrospinal fluid (CSF) and serum exosomes with diagnostic potential. One ml of CSF and serum sample were collected from each of the 30 untreated RRMS patients and healthy controls (HCs). A panel of 18 miRNAs affecting inflammatory responses was applied, and qRT-PCR was conducted to detect differentially expressed exosomal miRNAs in CSF and serum of RRMS patients. We identified that 17 out of 18 miRNAs displayed different patterns in RRMS patients compared to HCs. Let-7g-5p, miR-18a-5p, miR-145-5p, and miR-374a-5p with dual pro-inflammatory and anti-inflammatory actions and miR-150-5p and miR-342-3p with anti-inflammatory action were significantly upregulated in both CSF and serum-derived exosomes of RRMS patients compared to corresponding HCs. Additionally, anti-inflammatory miR-132-5p and pro-inflammatory miR-320a-5p were significantly downregulated in both CSF and serum-derived exosomes of RRMS patients compared to HCs. Ten of 18 miRNAs were differentially expressed in CSF and serum exosomes of the patients. Furthermore, miR-15a-5p, miR-19b-3p, and miR-432-5p were upregulated, and miR-17-5p was downregulated only in CSF exosomes. Interestingly, U6 housekeeping gene was differentially expressed in CSF and serum exosomes, in both RRMS and HCs. As the first report describing CSF exosomal miRNAs expression profile compared to that of serum exosomes in untreated RRMS patients, we showed that CSF and serum exosomes are not identical in terms of biological compounds and display different patterns in miRNAs and U6 expression.

Evaluation of Selected Oxidant/Antioxidant Parameters in Patients with Relapsing-Remitting Multiple Sclerosis Undergoing Disease-Modifying Therapies.

The aim of this study was to evaluate oxidative stress parameters, specifically the concentration of advanced oxidation protein products (AOPP) and ferric-reducing antioxidant power (FRAP), in the serum of patients with relapsing-remitting multiple sclerosis (RRMS). We also analyzed the relationships between each parameter and selected clinical/laboratory multiple-sclerosis-related parameters. The study group comprised 204 patients with RRMS and 29 healthy, age-matched controls. The concentration of AOPP was significantly higher in the RRMS patients than in controls. ROC analysis showed the ability of AOPP to distinguish between the patients with RRMS and controls (the value of AUC was 94.8%, with a sensitivity of 89.69% and specificity of 89.3%). AOPP and FRAP were significantly higher in male than in female RRMS patients. Correlations were found between AOPP and the laboratory markers of inflammation. AOPP differed in the subgroups of patients treated with particular medications. Our findings indicate an increase in the markers of oxidative stress in the serum of RRMS patients, possibly linked with chronic inflammation. Gender and type of treatment affected the markers of oxidative stress.

Increased Level of Caspase-1 in the Serum of Relapsing-remitting Multiple Sclerosis (RRMS) Patients.

Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system, in which proinflammatory cytokines play a critical role in the pathogenic formation of lesions. Caspase-1 is a cysteine protease that proteolytically cleaves precursors of interleukin (IL)-18 and IL-1β and turns them into their active forms. These inflammatory cytokines play an important role in the development of MS. The aim of the present study was the investigation of caspase-1 and its downstream products, IL-18 and IL-1β, in relapsing-remitting MS (RRMS) patients. In this study, we used an ELISA assay to measure serum and cellular caspase-1 and serum levels of IL-18 and IL-1β in RRMS patients in the relapse phase (n=23) and healthy age-and gender-matched controls (n=19). We observed that the caspase-1 level was significantly increased in the serum of MS patients compared to the healthy controls (p=0.03). Although caspase-1 concentration in the lysate of peripheral blood mononuclear cells (PBMCs) was higher than serum among patients and controls (p<0.001), no significant difference was found in cellular levels of caspase-1 between the two groups. There was no significant difference in serum levels of IL-18 and IL-1β between patients and controls. In this study, we found an elevation of extracellular caspase-1, as a reflection of its intracellular level, in the serum of RRMS patients during the relapse phase. Therefore, it suggests being a suitable peripheral biomarker of disease activity in multiple sclerosis.

Original article Evaluation of oxidative and nitrosative stress in relapsing remitting multiple sclerosis: effect of corticosteroid therapy

This study is designed to evaluate the roles of oxidative and nitrosative stress in serum and cerebrospinal fluid (CSF) of relapsing remitting multiple sclerosis (RRMS) patients. Oxidative stress markers thiobarbituric acid reactive substances (TBARS), 8-epi-PGF2α, conjugated diene and nitrosative stress markers nitrotyrosine, nitrit-nitrate were analysed in serum and CSF of 20 newly diagnosed RRMS patients before and after methyl prednysolone (MP) therapy (1000 mg/day i.v., for 5 days) and in healthy control group.TBARS and conjugated diene were analysed spectrophotometrically, nitrite-nitrate fluorometrically, 8-epi-PGF2α and nitrotyrosine were measured by ELISA. Serum conjugated diene (p < 0.001) and 8-epi-PGF2α (p < 0.05) levels were significantly higher in RRMS patients before MP therapy with respect to control group. MP therapy caused a significant decrease only in 8-epi-PGF2α level (p < 0.05). Serum nitrotyrosine levels were significantly lower in RRMS patients both before (p < 0.001) and after (p < 0.001) MP therapy with respect to controls. Serum nitrite-nitrate levels were significantly lower (p < 0.05) in RRMS patients before therapy compared to controls. Nitrotyrosine and nitrite-nitrate levels in CSF of RRMS patients were significantly higher (p < 0.001) before therapy compared to normal pressure hydrocephalia control group. Our findings reveal increased oxidative stress in serum of RRMS patients and the benefical role of MP therapy in relieving oxidative stress.As to nitrosative stress, nitrotyrosine and nitrite-nitrate levels were increased in CSF and decreased in serum.

Serum ganglioside patterns in multiple sclerosis.

The relative distribution of gangliosides was determined in the serum of 37 patients with multiple sclerosis (MS) and of 30 healthy subjects. There was a significant increase of GM1 and GD1a, and a decrease of GM3 proportion in the serum of relapsing-remitting MS patients (RRMS) during their first MS attack. The RRMS patients in relapse with a long duration of the disease had a significant decrease of GM1 and an increase of GD1a portion in the serum. An increase of GD1a, one of the major brain neuron ganglioside fraction, suggested the neuron injury in the early and with a long duration RRMS. The finding of an increase of GM1, the main human myelin ganglioside, during the first MS attack in RRMS patients confirms previous evidence for the possible involvement of gangliosides in the early pathological course of demyelination in MS.