Levels In Multiple Sclerosis Patients Research Articles

Serum BAFF levels, Methypredsinolone therapy, Epstein-Barr Virus and Mycobacterium avium subsp. paratuberculosis infection in Multiple Sclerosis patients.

Elevated B lymphocyte activating factor BAFF levels have been reported in multiple sclerosis (MS) patients; moreover, disease-modifying treatments (DMT) have shown to influence blood BAFF levels in MS patients, although the significance of these changes is still controversial. In addition, BAFF levels were reported increased during infectious diseases. In our study, we wanted to investigate on the serum BAFF concentrations correlated to the antibody response against Mycobacterium avium subspecies paratuberculosis (MAP), Epstein-Barr virus (EBV) and their human homologous epitopes in MS and in patients affected with other neurological diseases (OND), divided in Inflammatory Neurological Diseases (IND), Non Inflammatory Neurological Diseases (NIND) and Undetermined Neurological Diseases (UND), in comparison to healthy controls (HCs). Our results confirmed a statistically significant high BAFF levels in MS and IND patients in comparison to HCs but not NIND and UND patients. Interestingly, BAFF levels were inversely proportional to antibodies level against EBV and MAP peptides and the BAFF levels significantly decreased in MS patients after methylprednisolone therapy. These results implicate that lower circulating BAFF concentrations were present in MS patients with humoral response against MAP and EBV. In conclusion MS patients with no IgGs against EBV and MAP may support the hypothesis that elevated blood BAFF levels could be associated with a more stable disease.

Racial Variations in Mean Serum Vitamin A (Retinoic Acid) Levels in Multiple Sclerosis Patients with Normal/Corrected Vitamin D Levels (P3.012)

Racial Variations in Mean Serum Vitamin A (Retinoic Acid) Levels in Multiple Sclerosis Patients with Normal/Corrected Vitamin D Levels (P3.012)

Natural Triterpene Glycosides for Antibody Recognition

Multiple sclerosis is an autoimmune disease that affects the central nervous system. The key role of the glycosylation in disease pathogenesis has been previously studied and the synthetic N-glucosylated peptide CSF114(Glc) proved its efficiency in autoantibody recognition in the sera of multiple sclerosis patients. Herein, pure natural triterpene glycosides containing different glycosyl moieties were isolated and tested in multiple sclerosis patientsʼ sera to better understand the role of glycosylation. They were selected taking into account the nature and complexity of their osidic part. Five triterpene glycosides were isolated from several plants with more than 95 % purity. The interaction between these glycosides and autoantibodies was evaluated in an enzyme-linked immunosorbent assay measuring IgG and IgM levels in multiple sclerosis patients and healthy blood donors, and the results were compared with those of CSF114(Glc). For each antigen, Mann Whitney and receiver operating characteristic-based analysis were performed to evaluate any statistical significance of the results. The five natural triterpene glycosides showed good capacity to recognize IgMs (sensitivity up to 38 %) with a high specificity (88.9 %) for multiple sclerosis patients.

Effects of vitamin D deficiency on the relapse, severity, and disability of multiple sclerosis

Background Multiple sclerosis (MS) is a long-standing inflammatory disease of the white matter and affects more than two million people worldwide. Upcoming evidence proposed that 25-hydroxy-vitamin D 3 (25HVD 3 ) deficiency could be one of the most crucial environmental elements for the pathogenesis of MS. Objective The aim of this study was to compare 25HVD 3 levels in MS patients and controls and to detect the association with relapse, severity, and disability in MS patients. Patients and methods Mansoura Neurology Department data sheet was collected and all patients were assessed using the Expanded Disability Status Scale (EDSS) at the onset. 25HVD 3 levels in the blood were evaluated for all patients and controls using the chemiluminescent immunoassay test. Results A total of 50 MS patients were included in this work and matched with 25 controls. There was a statistically significantly lower mean serum 25HVD 3 level in MS patients in comparison with the controls (20.5 ± 16.8 and 42.9 ± 17.9 ng/ml, respectively; P = 0.002). In addition, there was a statistically significantly lower level of 25HVD 3 (18.4 ± 17.7) in severe cases of MS (EDSS ≥ 6; P P P 3 deficiency ( Conclusion Our results showed that there is an inverse correlation between 25HVD 3 level and EDSS score. In addition, lower 25HVD 3 levels are associated with increased relapse risk in MS.

Serum Gelatinases Levels in Multiple Sclerosis Patients during 21 Months of Natalizumab Therapy.

Background. Natalizumab is a highly effective treatment approved for multiple sclerosis (MS). The opening of the blood-brain barrier mediated by matrix metalloproteinases (MMPs) is considered a crucial step in MS pathogenesis. Our goal was to verify the utility of serum levels of active MMP-2 and MMP-9 as biomarkers in twenty MS patients treated with Natalizumab. Methods. Serum levels of active MMP-2 and MMP-9 and of specific tissue inhibitors TIMP-1 and TIMP-2 were determined before treatment and for 21 months of therapy. Results. Serum levels of active MMP-2 and MMP-9 and of TIMP-1 and TIMP-2 did not differ during the treatment. The ratio between MMP-9 and MMP-2 was increased at the 15th month compared with the 3rd, 6th, and 9th months, greater at the 18th month than at the 3rd and 6th months, and higher at the 21st than at the 3rd and 6th months. Discussion. Our data indicate that an imbalance between active MMP-9 and active MMP-2 can occur in MS patients after 15 months of Natalizumab therapy; however, they do not support the use of serum active MMP-2 and active MMP-9 and TIMP-1 and TIMP-2 levels as biomarkers for monitoring therapeutic response to Natalizumab.

The influence of catecholamines on Th17-cells in multiple sclerosis

Тo investigate the possible association between clinical characteristics of multiple sclerosis (MS), quantitative and qualitative characteristics of Th17, dopamine and norepinephrine concentrations in the serum in patients with multiple sclerosis (MS). A comprehensive neurological and immunological examination of 43 patients with relapsing-remitting-MS (RR-MS) was performed. All patients were subjected to a standard neurological examination with assessment of the EDSS score. Dopamine and norepinephrine concentrations in serum were measured by enzyme-linked immunosorbent assay (ELISA). Percentage of Th17-cells was determined by flow cytometry. The functional activity of Th17- and Th1-cells was assessed by the production of interleukin-17 (IL-17) and interferon-gamma (IFN-γ), respectively, by peripheral blood mononuclear cells (PBMC) stimulated with microbeads coated with anti-CD3 and anti-CD28-antibodies. The percent Th17-cells and cytokine production was significantly higher in MS patients with the exacerbation of disease than in the control group or remission, while the dopamine level was lower. Norepinephrine levels in MS patients in the acute stage and remission were comparable, but nevertheless, reliably lower than in the control group. The results suggest the inhibitory effect of catecholamines on Th17 cells.

Changes in Blood B Cell-Activating Factor (BAFF) Levels in Multiple Sclerosis: A Sign of Treatment Outcome

Multiple sclerosis (MS) is mediated primarily by autoreactive T cells. However, evidence suggesting the involvement of humoral immunity in brain diseases has increased interest in the role of B cells and their products during MS pathogenesis. The major survival factor for B cells, BAFF has been shown to play a role in several autoimmune conditions. Elevated BAFF levels have been reported in MS animal model and during MS relapse in patients. Moreover, disease-modifying treatments (DMT) reportedly influence blood BAFF levels in MS patients, but the significance of these changes remains unclear. The present study addresses how blood BAFF levels are associated with the clinical course of relapsing-remitting MS and the effectiveness of DMT and short-term steroid treatment. During a prospective longitudinal follow-up of 2.3 years, BAFF was measured in the blood of 170 MS patients in the stable phase and within 186 relapses. BAFF levels were significantly higher in MS patients compared to healthy controls. However, stable MS patients without relapses exhibited significantly higher BAFF levels than relapsing patients. Treatment with interferon-β and immunosuppressants raised BAFF blood levels. Interestingly, a similar effect was not seen in patients treated with glatiramer acetate. Short-term treatment with high doses of intravenous methylprednisolone did not significantly alter plasma BAFF levels in 65% of relapsing-remitting MS patients. BAFF were correlated weakly but significantly with monocyte and basophil counts, but not with other blood cell types (neutrophils, lymphocytes, or eosinophils) or inflammatory biomarkers. To our knowledge, this is the first report demonstrating that higher blood BAFF levels may reflect a more stable and effective MS treatment outcome. These results challenge hypotheses suggesting that elevated blood BAFF levels are associated with more severe disease presentation and could explain the recent failure of pharmaceutical trials targeting BAFF with soluble receptor for MS treatment.

Identifying clues to molecular etiology of multiple sclerosis in South Indian patients

BackgroundEnvironmental risk factors have a dominant role in the pathogenesis of multiple sclerosis (MS). Unhealthy lifestyle can predispose people to autoimmune diseases. MS was a rare disease in Kerala, but now, we notice frequent cases of MS at the city neurology clinic. Changing lifestyle and associated changes in the level of proinflammatory biomolecules like: leptin, soluble leptin receptor (SLR) and free fatty acids (FA) could be contributing to rise in MS incidence. ObjectiveTo identify variations in the levels of bio-molecules: leptin, SLR and FA, between MS patients and matched healthy control. Method: Leptin and SLR levels in the blood serum, were estimated using ELISA, while total FA levels, were estimated using an enzyme based calorimetric assay. ResultMean serum FA levels in MS patients (31.39±4.83nmole/100μl) were 2.7 fold higher than controls (11.54±2.66nmoles/100μl) at more than 99% CI. The differences in mean leptin and SLR levels were not statistically significant. ConclusionMS patients had high level of total FA in their blood. High FA in blood may have a role in MS pathogenesis. More in-depth study is required to understand the precise mechanism by which FA rise in MS blood sample can contribute to pathogenesis.

Short-Term Effect of High-Dose Vitamin D on the Level of Interleukin 10 in Patients with Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Background: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. Vitamin D has been related to the prevention of MS and to modulating its course. Recent studies have shown the safety of high-dose vitamin D in MS. Objective: This study compared the effects of high-dose vitamin D on interleukin 10 (IL-10) levels in MS patients in a double-blind, randomized clinical trial. Methods: Ninety-four patients with relapsing remitting MS (RRMS) were randomized into a treatment and a placebo group. Both groups received conventional MS treatment. The intervention group received 50,000 IU of vitamin D every 5 days for 3 months. IL-10 was measured at baseline and after 3 months. Results: Serum levels of IL-10 were (median ± IQR): 12.58 ± 11.97 and 10.97 ± 9.97 pg/ml in the intervention and placebo groups, respectively, at baseline (p = 0.161); after 3 months, these levels were 13.76 ± 18.95 and 11.31 ± 19.63 pg/ml, respectively (p = 0.158). The IL-10 level increased significantly after receiving high-dose vitamin D for 3 months (β = 0.737, p = 0.015 and R² = 0.91). Conclusion: IL-10 levels increased significantly in RRMS patients after taking high-dose vitamin D₃ for 3 months. High-dose vitamin D might be useful in promoting an anti-inflammatory state in RRMS patients.

Effect of high dose vitamin D intake on interleukin-17 levels in multiple sclerosis: A randomized, double-blind, placebo-controlled clinical trial

BackgroundVitamin D has immunomodulatory effects in multiple sclerosis (MS). Vitamin D acts through various mechanisms such as secretion of cytokines. Interleukin-17 (IL-17) is a critical interleukin in inflammatory response in MS. ObjectiveThis study assessed the effect of oral high dose vitamin D intake on IL-17 levels in MS patients in a double blind randomized clinical trial. Methods94 patients with a diagnosis of relapsing remitting multiple sclerosis (RRMS) were randomized to two groups. One group received 50,000 IU vitamin D3 every five days for 12weeks. The other group was given placebo. Both groups received interferon-β (IFN-β) treatment. Serum levels of IL-17 were measured at the beginning of the study and after 12weeks. ResultsIL-17 serum levels were 56.75±28.72pg/ml and 30.31±75.85pg/ml in the intervention and placebo group at the beginning of the study, respectively (Median±IQR, p=0.338). After 12weeks, IL-17 levels were 58.93±67.93pg/ml and 46.13±94.70pg/ml in the intervention and placebo group, respectively (Median±IQR, p=0.960). The multiple linear regression analysis indicated that the consumption of vitamin D3 was positively and significantly associated with the logarithm of IL-17 measures (β=1.719; p=0.002 and R2=0.91), adjusted by EDSS scores. ConclusionIL-17 levels showed significant change in RRMS patients after receiving high dose vitamin D3 for 12weeks.

Association of copeptin and cortisol in newly diagnosed multiple sclerosis patients.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. Obesity may increase the risk of developing MS. The aim of this study was to evaluate copeptin and cortisol plasma levels in newly diagnosed untreated MS patients and to determine whether copeptin and cortisol are related to the patients' clinical statuses. We report that copeptin and cortisol were higher in overweight/obese MS patients. Positive correlations were observed between the two parameters. We conclude that alterations of copeptin and cortisol levels in multiple sclerosis patients may be related to adiposity. An increase in cortisol may also be associated with copeptin secretion.

Fatigue in patients with multiple sclerosis: From movement preparation to motor execution

BackgroundThe neural mechanisms underlying fatigue in multiple sclerosis (MS) are still poorly understood. Cortico-cortical and cortico-subcortical circuitry abnormalities may play a central role in its pathogenesis. Our previous studies suggest that central fatigue may be related to an impairment of volition drive during movement preparation. ObjectiveWe further explored the central mechanisms of fatigue at the premovement level in MS patients during a sustained motor task. MethodsIn MS patients with (MS-F) and without (MS-NF) fatigue and age-matched healthy controls, we evaluated the motor cortex excitability and the premovement facilitation (PMF) through transcranial magnetic stimulation before and after 5min of sequenced finger-tapping movements at a fixed frequency of 2Hz. ResultsIn MS-F patients, the number of correct sequences performed and the ability to keep a fixed movement rate during the 5-min motor task were significantly decreased in comparison to the normal controls and MS-NF patients. Also, in MS-F patients, post-exercise PMF was significantly decreased. The PMF abnormalities were highly correlated with the performance decay. ConclusionsPMF may be considered as a kind of servo-mechanism which could play a crucial role during sustained motor task in order to prevent motor performance disruption and to avoid motor exhaustion.

Relationship between the Increased Haemostatic Properties of Blood Platelets and Oxidative Stress Level in Multiple Sclerosis Patients with the Secondary Progressive Stage.

Multiple sclerosis (MS) is the autoimmune disease of the central nervous system with complex pathogenesis, different clinical courses and recurrent neurological relapses and/or progression. Despite various scientific papers that focused on early stage of MS, our study targets selective group of late stage secondary progressive MS patients. The presented work is concerned with the reactivity of blood platelets in primary hemostasis in SP MS patients. 50 SP MS patients and 50 healthy volunteers (never diagnosed with MS or other chronic diseases) were examined to evaluate the biological activity of blood platelets (adhesion, aggregation), especially their response to the most important physiological agonists (thrombin, ADP, and collagen) and the effect of oxidative stress on platelet activity. We found that the blood platelets from SP MS patients were significantly more sensitive to all used agonists in comparison with control group. Moreover, the platelet hemostatic function was advanced in patients suffering from SP MS and positively correlated with increased production of O2 −∙ in these cells, as well as with Expanded Disability Status Scale. We postulate that the increased oxidative stress in blood platelets in SP MS may be primarily responsible for the altered haemostatic properties of blood platelets.

Decreased endothelin-1 plasma levels in multiple sclerosis patients: a possible factor of vascular dysregulation?

BackgroundMultiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system with possible involvement of vascular dysregulation secondary to endothelial dysfunction caused by destruction of the vessel wall. Vascular dysregulation leads to excessive vasoconstriction or insufficient vasodilatation, resulting in vasospasm mediated by endothelin-1 (ET-1), the most potent and long-lasting mediator. Vascular dysregulation can play an important role in the pathogenesis of some eye disorders and it has been hypothesized that it is a vascular risk factor for glaucomatous optic neuropathy. The aim of this study was to estimate endothelin-1 (ET-1) plasma levels in patients with MS.Material/MethodsThe MS group consisted of 39 patients (9 males, 30 females), mean age: 38.8±10.02 years, range: 22–62. The control group consisted of 27 healthy volunteers (3 males and 24 females), mean age: 37.4±10.88 years, range: 20–62; clinically, in a non-active stage of the disease. ET-1 plasma levels were measured using the Endothelin-1 ELISA Kit (Immuno-Biological Laboratories Co., Japan). Statistical analysis was performed with the nonparametric Mann-Whitney U test for independent groups.ResultsEndothelin-1 (ET-1) plasma levels were significantly lower in MS patients compared to healthy controls: mean value 0.55±0.44 pg/ml (146.05±118.27 fmol/ml) vs. 0.95±0.48 pg/ml (252.83±127.16 fmol/ml); P=0.012.ConclusionsSignificantly decreased ET-1 plasma levels in the MS patients could reflect the non-active disease at the time of ET-1 measurements or the effects of immunomodulatory treatment, but it cannot be excluded that decreased ET-1 plasma levels in these patients might result from vascular dysregulation.

P017 - Role of microchimeric cells in pathogenesis of multiple sclerosis

Background Multiple sclerosis (MS) is a chronic neuroinflammatory disease of central nervous system (CNS). Although the exact etiology of MS in not fully known, it has been shown that an interaction of environmental and genetic factors are involved. During pregnancy maternal and fetal cells commute back and forth leading to fetal microchimerism in the mother and maternal microchimerism in the child that can persist for years and contribute in pathogenesis of autoimmune diseases. Thus, in this study we aimed to measure levels of microchimeric cells in blood of MS patients. Methods In a case control study, blood was collected from women with diagnosis of definite MS (n=40) and healthy women as control group (n=40). DNA was extracted and microchimeric cell level measurement was performed using quantitive Real-Time PCR. Results Microchimeric cell level in MS patients was significantly higher than control subjects (p?0.05). Conclusions Our results suggested that microchimeric cells have a role in pathogenesis of MS although, further evidence will be required to establish this cells as a modifier in the risk of MS.

Short term fingolimod treatment decreases soluble VLA 4 levels in MS patients

Multiple sclerosis (MS) is an immune mediated disorder of the central nervous system. T-cells and other immune effector cells play crucial roles in MS pathogenesis by crossing the brain–blood barrier and consequently destroying the myelin sheat and axons. Fingolimod (FTY720) is an oral sphingosine-1-phosphate (S1P) receptor modulator, approved for treatment of MS. Resting T and B lymphocytes express elevated levels of S1P receptor and lymphocyte migration from the lymphoid organs to the brain depends on the activity of this receptor.

CD8⁺ MAIT cells infiltrate into the CNS and alterations in their blood frequencies correlate with IL-18 serum levels in multiple sclerosis.

Recent findings indicate a pathogenic involvement of IL-17-producing CD8(+) Tcells in multiple sclerosis (MS). IL-17 production has been attributed to a subset of CD8(+) Tcells that belong to the mucosal-associated invariant T (MAIT) cell population. Here, we report a reduction of CD8(+) MAIT cells in the blood of MS patients compared with healthy individuals, which significantly correlated with IL-18 serum levels in MS patients. In vitro stimulation of peripheral blood mononuclear cells from healthy individuals and MS patients with IL-18 specifically activated CD8(+) MAIT cells. Moreover, IL-18 together with T-cell receptor stimulation induced, specifically on CD8(+) MAIT cells, an upregulation of the integrin very late antigen-4 that is essential for the infiltration of CD8(+) Tcells into the CNS. Notably, we were able to identify CD8(+) MAIT cells in MS brain lesions by immunohistochemistry while they were almost absent in the cerebrospinal fluid (CSF). In summary, our findings indicate that an IL-18-driven activation of CD8(+) MAIT cells contributes to their CNS infiltration in MS, in turn leading to reduced CD8(+) MAIT-cell frequencies in the blood. Therefore, CD8(+) MAIT cells seem to play a role in the innate arm of immunopathology in MS.

Correlation of midkine serum level with pro- and anti-inflamatory cytokines in multiple sclerosis.

Midkine (MK) is a heparin-binding growth factor with promoting effects in inflammatory responses through enhancing leukocytes migration. To study the correlation between MK serum levels and concentration of inflammatory cytokines in Multiple Sclerosis (MS) patients. We evaluated the MK level and its relationship with inflammatory cytokines (IL-17 and IL-23) and anti-inflammatory ones (IL-10 and TGF-β) in multiple sclerosis (MS) patients. The serum concentrations of MK and cytokines were assessed by ELISA in 32 MS patients in comparison with 32 healthy subjects. Our data showed that the MK concentration in MS patients is lower than healthy controls (341.15 ± 40.71 Pg/ml vs. 620.15 ± 98.61 Pg/ml, respectively, p=0.015). We also observed a significant decrease in IL-10, IL-23, and TGF-β cytokine levels in MS patients. There was a significant correlation between MK and IL-23 concentrations in our study (r = +0.829, p≤ 0.001). These results confirm a role for MK in inflammatory reactions in MS.

BAb and MxA as Functional Biomarkers in Routine Clinical Laboratories for the Determination of Anti-IFN-Beta Antibodies and Their Bioactivity Levels in Multiple Sclerosis Patients

In MS patients under IFNβ treatment to seek alternative treatments timely is important that anti-IFNβ antibodies and/or in vivo biologic activity loss detection in these. The most common diagnostic markers used for this purpose are BAb, Nab, and MxA. In this article, we aimed to establish the availability and feasibility of the correlation between BAb and MxA gene expression (mRNA) levels using evaluation of responses to IFNβ treatment for MS patients with a routine laboratory follow-up strategy in a major Turkish MS center. Bab seropositivity was determined in blood samples of 218 MS patients treated with different IFNβ preparations and MxA mRNA levels were measured in 128 patients among the total population. BAb seropositivity ratios to im INF-β 1a, scINF-β 1a, and sc INF-β 1b were 21.4%, 28.6%, and 70.4%, respectively (total 40%), and total loss of bioactivity (MxA mRNA) were 9.3%, 9.5%, and 11.6%, respectively (total 10.2%). The correlation between high BAb titers and low MxA mRNA levels was highly significant (P = 0.00003). Our data indicate that there is a good correlation between especially high BAbs levels and diminished MxA mRNA levels.

Serum phosphorylated neurofilament-heavy chain levels in multiple sclerosis patients

ObjectivesWe evaluated whether the measurement of serum phosphorylated neurofilament heavy chain (pNF-H) titre is likely to be a valid biomarker of axonal injury in multiple sclerosis (MS).MethodsSerum pNF-H concentrations were...