Clinical and Serological Biomarkers of Treatment’s Response in Multiple Sclerosis Patients Treated Continuously with Interferonβ-1b for More than a Decade

2018 ◽  
Vol 17 (10) ◽  
pp. 780-792 ◽  
Author(s):  
Laura Iulia Bărcuţean ◽  
Andreea Romaniuc ◽  
Smaranda Maier ◽  
Zoltan Bajko ◽  
Anca Moţăţăianu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Demographic Data ◽  
Active Form ◽  
Positive Influence ◽  
Serum Samples ◽  
Disability Score ◽  
Positive Correlations ◽  
Multiple Sclerosis Patients ◽  
Factor Α ◽  
Serological Biomarkers

Introduction: We evaluated the peripheral immune panel of Multiple Sclerosis (MS) patients treated for more than 10 years with interferon-beta1b (IFNβ-1b) and aimed to identify possible biomarkers of treatment response. Material and Methods: Serum samples from 70 MS patients treated with IFNβ-1b more than a decade were analysed for 15 cytokines, that were correlated with the disability score, annual relapse ratio (ARR): the total number of relapses-ARR_0, relapse on treatment-ARR_1 and demographic data. Two groups were defined based on the levels of disability, calculated using the Expanded Disability Status Scale (EDSS): G1 – recurrent-remissive and G2 – secondary-progressive. Furthermore, we split the patients based on gender (G1_f, G1_m, G2_f, G2_m). Results: The ARR was reduced after treatment was instituted. We found positive correlations between IL_25 and EDSS in G1_f and G2_f, tumor necrosis factor α (TNFα) and ARR_1 and ARR_0 in G1, and IL_17F with ARR_1. Negative correlations were for IL_25 and ARR_0 and ARR_1. SCD40L intensely positively correlated with IL_31 in G1 and G2. Conclusion: After more than a decade of treatment, IFNβ-1b offers good results by reducing relapses and slowing disability progression. Several biomarkers can be used to assess the patient’s response. High levels of IL_17 and TNFα will indicate a more active form of the disease. IL-25 may exert a positive influence in male MS patients and should be considered for future studies, together with the co-modulation between sCD40L and IL_31. Our method allowed us to screen the peripheral immune panel and can be used for assessing the peripheral levels of the above-mentioned cytokines.

Assessment of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D3 concentrations in male and female multiple sclerosis patients and control volunteers

2007 ◽  
Vol 13 (5) ◽  
pp. 670-672 ◽  
Author(s):  
M.S. Barnes ◽  
M.P. Bonham ◽  
P.J. Robson ◽  
J.J. Strain ◽  
A.S. Lowe-Strong ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Active Form ◽  
Plasma Concentrations ◽  
Secondary Analysis ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Multiple Sclerosis Patients ◽  
And Control

Populations with insufficient ultraviolet exposure and who consume diets low in vitamin D have low vitamin D status (plasma 25-hydroxyvitamin D (25(OH)D) concentrations) and a reported higher incidence of multiple sclerosis (MS). The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is an effective anti-inflammatory molecule. No research to date has assessed 1,25(OH)2D3 concentrations in individuals with MS. In this study, plasma concentrations of 25(OH)D, 1,25(OH)2D 3 and parathyroid hormone (PTH) were measured in 29 individuals with MS and 22 age- and sex-matched control volunteers. There were no significant differences in plasma PTH, 25(OH)D and 1,25(OH)2D3 concentrations between individuals with MS and control volunteers. Women with MS had significantly higher 25(OH)D and 1,25(OH)2D3 concentrations than men with MS (79.1 ±45.4 versus 50.2±15.3 nmol/L, P=0.019 and 103.8± 36.8 versus 70.4±28.7 pmol/L, P=0.019, respectively). There was a significant positive correlation between 25(OH)D and 1,25(OH)2D 3 concentrations in all subjects (r=0.564, P=0.000), but secondary analysis revealed that the correlation was driven by women with MS (r=0.677, P= 0.001). Significant sex differences in vitamin D metabolism were observed and were most marked in individuals with MS, suggesting that vitamin D requirements may differ between the sexes, as well as by underlying disease state. Multiple Sclerosis 2007; 13: 670-672. http://msj.sagepub.com

scholarly journals Accurate classification of secondary progression in multiple sclerosis

2020 ◽  
Author(s):  
Ryan Ramanujam ◽  
Feng Zhu ◽  
Katharina Fink ◽  
Virginija Danylaite Karrenbauer ◽  
Johannes Lorscheider ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
British Columbia ◽  
Randomized Clinical Trials ◽  
Disease Phenotype ◽  
Disability Score ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients ◽  
Clinical Records ◽  
Independent Cohort

Transition from a relapsing-remitting to the secondary progressive phenotype is an important milestone in the clinical evolution of multiple sclerosis. In the absence of reliable imaging or biological markers of phenotype transition, assignment of current phenotype status relies on retrospective evaluation of the medical history of an individual. Here, we sought to determine if demographic and clinical information from multiple sclerosis patients can be used to accurately assign current disease phenotypes: either relapsing-remitting or secondary progressive status. Data from the most recent clinical visit of 14,387 multiple sclerosis patients were extracted from the Swedish Multiple Sclerosis Registry. Decision trees based on sex, symptom onset age, Expanded Disability Scale Status score, and age & disease duration at the most recent clinic visit, were examined to build a classifier to determine disease phenotype. Validation was conducted using an independent cohort of multiple sclerosis patients from British Columbia, Canada, and a previously published classifier to assign phenotype was also tested. Clinical records of 100 randomly selected patients were used to manually categorize phenotype by three independent neurologists. A decision tree (the classifier) containing only most recently available disability score and age obtained 89.3% (95% confidence intervals (CI): 88.8% to 89.8%) classification accuracy, defined as concordance with the latest reported status in the registry. Replication in an independent cohort from British Columbia resulted in 82.0% (95%CI: 81.0% to 83.1%) accuracy. A previously published classification algorithm with slight modifications achieved 77.8% (95%CI: 77.1% to 78.4%) accuracy when assigning disease phenotype. With complete patient history data, three neurologists obtained 84.7% accuracy on average compared with 85 for the classifier using the same data. The model is easily interpretable and could allow research studies and randomized clinical trials to estimate the probability of patients having already reached the secondary progressive stage when they have not yet been retrospectively assigned this status, and to standardize definitions of disease phenotype across different cohorts. Clinically, this model could assist neurologists by providing additional information about the probability of having secondary progressive disease. This could also benefit patients who may be introduced to new therapies targeting progressive multiple sclerosis.

Interleukin-12 and tumor necrosis factor-α levels in cerebrospinal fluid of multiple sclerosis patients

1997 ◽  
Vol 147 (2) ◽  
pp. 145-150 ◽  
Author(s):  
Jelena Drulović ◽  
Marija Mostarica-Stojković ◽  
Zvonimir Lević ◽  
Nebojša Stojsavljević ◽  
Vera Pravica ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Interleukin 12 ◽  
Multiple Sclerosis Patients ◽  
Factor Α ◽  
Necrosis Factor

Lesions by tissue specific imaging characterize multiple sclerosis patients with more advanced disease

2011 ◽  
Vol 17 (12) ◽  
pp. 1424-1431 ◽  
Author(s):  
Francesca Bagnato ◽  
Vasiliki N Ikonomidou ◽  
Peter van Gelderen ◽  
Sungyoung Auh ◽  
Jailan Hanafy ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Advanced Disease ◽  
Spin Echo ◽  
Brain Parenchyma ◽  
Lesion Volume ◽  
Tissue Destruction ◽  
Disability Score ◽  
Tissue Specific ◽  
Volumetric Images ◽  
Multiple Sclerosis Patients

Background: Cerebrospinal fluid tissue specific imaging (CSF-TSI), a newly implemented magnetic resonance imaging (MRI) technique, allows visualization of a subset of chronic black holes (cBHs) with MRI characteristics suggestive of the presence of CSF-like fluid, and representing lesions with extensive tissue destruction. Objective: To investigate the relationship between lesions in CSF-TSI and disease measures in patients with multiple sclerosis (MS). Methods: Twenty-six patients with MS were imaged at 3.0 T, obtaining T1-weighted (T1-w) and T2-w spin echo (SE), T1 volumetric images and CSF-TSI images. We measured: (i) lesion volume (LV) in T1-w (cBH-LV) and T2-w SE images, and in CSF-TSI; (ii) brain parenchyma fraction (BPF). Differences between patients with and without CSF-TSI lesions were analyzed and association between clinical and MRI metrics were investigated. Results: cBHs were seen in 92% of the patients while lesions in CSF-TSI were seen in 40%. Patients with CSF-TSI lesions were older, with longer disease duration, higher disability scores, larger cBH-LV and T2-LV, and lower BPF than patients without CSF-TSI lesions (≤0.047). Partial correlation analysis correcting for T2-LV, cBH-LV and BPF showed an association ( p < 0.0001, r = 0.753) between CSF-TSI LV and disability score. Conclusions: CSF-TSI lesions characterize patients with more advanced disease and probably contribute to the progress of disability.

Serum immunologic markers in multiple sclerosis patients on continuous combined therapy with beta-interferon 1a, prednisone and azathioprine

2006 ◽  
Vol 12 (5) ◽  
pp. 652-658 ◽  
Author(s):  
C A Braun Hashemi ◽  
Y CQ Zang ◽  
J A Arbona ◽  
J A Bauerle ◽  
M L Frazer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Serum Level ◽  
Serum Concentration ◽  
Combined Therapy ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Beta Interferon ◽  
Immunologic Markers ◽  
Multiple Sclerosis Patients ◽  
Factor Α

Break-through symptoms (BTS) in multiple sclerosis (MS) patients on beta-interferon (beta-IFN) monotherapy are most frequently treated with a brief administration of steroids. Here, we report the results of monitoring serum immunologic markers recorded at three-month intervals for 1.5 years in responders to beta-INF 1a (Avonex) monotherapy ( n = 21) and MS patients placed on Avonex with prednisone ( n = 83) and Avonex, prednisone and azathioprine (AZA) ( n = 21) because of BTS. Compared to 23 healthy controls, patients on Avonex monotherapy and Avonex with prednisone, in individuals on Avonex, prednisone and AZA, a significant decrease in serum concentration of soluble intercellular adhesion molecule-1 (sICAM-1) ( P = 0.001) was established. Combined therapy with Avonex, prednisone and AZA was associated with a significant increase in the serum level of interleukin (IL)10 ( P < 0.001). Compared to Avonex monotherapy, combined therapy suppressed the serum level of IL12p40, antagonized elevation in the serum concentration of soluble IL2 receptor (sIL2R) and inhibited an increase in the serum soluble CD95 (sCD95) molecule. In patients studied, no significant differences in the serum level of IL18 and tumor necrosis factor-α (TNF-α) were established. These findings are important in understanding some of the immunoregulatory mechanisms induced by combined therapy in MS.

Tumor Necrosis Factor-α-308 Gene Polymorphism in Croatian and Slovenian Multiple Sclerosis Patients

2007 ◽  
Vol 57 (4) ◽  
pp. 203-207 ◽  
Author(s):  
Smiljana Ristić ◽  
Luca Lovrečić ◽  
Nada Starčević-Čizmarević ◽  
Bojana Brajenović-Milić ◽  
Saša Šega Jazbec ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Tumor Necrosis Factor ◽  
Gene Polymorphism ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Multiple Sclerosis Patients ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals The Main Determinants for Suicidal Ideation in a Romanian Cohort of Multiple Sclerosis Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Andreea Romaniuc ◽  
Rodica Bălaşa ◽  
Nicoleta Ştirbu ◽  
Smaranda Maier ◽  
Sebastian Andone ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Occupational Status ◽  
Related Information ◽  
Disease Modifying Therapy ◽  
Functional Scores ◽  
Disability Status ◽  
Main Determinants ◽  
Positive Correlations ◽  
Multiple Sclerosis Patients ◽  
Disability Level

Objective. To determine the prevalence of suicidal concerns (SC) in a large multiple sclerosis (MS) patient group and to assess the major determinants that are implicated in their occurrence. Methods. A total of 349 patients were included in the study. They completed a survey about their demographic characteristics, psycho-socio-economic data, and disease-related information. Their disability level was assessed using the Expanded Disability Status Scale (EDSS) based on the neurological examination performed by the same doctor for every patient and the SC were documented with the Beck Depression Inventory-II questionnaire. Results. The study included 112 men and 237 women, with a mean age around 42 years old. Suicidal thoughts were more frequent in men, while suicidal intentions in women. Positive correlations were found between SC and depression, EDSS, total number of relapses, disease duration, and level of education. From the EDSS functional scores, only the pyramidal score and the cerebellar score presented a significant correlation with SC. None of the patients with clinically isolated syndrome had SC. The type of disease-modifying therapy, marital and occupational status, and the presence of children did not influence the presence of SC. Conclusions. The prevalence of SC is higher in patients with MS compared to the general population. Their occurrence is mostly influenced by the disease itself (duration, relapses, acquired disability) and also by depression and lack of education.

Neurofilament Light Chain Levels Are Associated with Disease Activity Determined by No Evident Disease Activity in Multiple Sclerosis Patients

2021 ◽  
pp. 1-8
Author(s):  
Jarmila Szilasiová ◽  
Jaroslav Rosenberger ◽  
Miriam Fedičová ◽  
Pavol Mikula ◽  
Peter Urban ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Disease Activity ◽  
Sensitivity And Specificity ◽  
Light Chain ◽  
Operating Characteristics ◽  
Disability Score ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Multiple Sclerosis Patients

<b><i>Introduction:</i></b> There is a need for blood biomarkers of disease activity in multiple sclerosis (MS). The aim of the study was to assess the relationship between plasma neurofilament light chain (pNfL) and disease activity as defined by the concept three-domain no evident disease activity (NEDA-3). <b><i>Methods:</i></b> Levels of pNfL (SIMOA) were examined in 159 MS patients and analyzed in relationship to NEDA-3 status (absence of relapse, disability score worsening, and brain magnetic resonance activity) during the last 12 months. The accuracy of the proposed model was evaluated by calculating the area under the receiver operating characteristics (ROC) curve. From the pNfL cutoff, we evaluated the NEDA-NfL status (no relapse, no Expanded Disability Status Scale [EDSS] worsening, and pNfL below the cutoff value). <b><i>Results:</i></b> Levels of pNfL were significantly higher in MS patients than in healthy controls (<i>p</i> &#x3c;  0.001). From a total of 159 patients, 80 (50.3%) achieved NEDA-3 status, while 79 (49.7%) patients showed evident disease activity (EDA) status. pNfL were significantly lower in the NEDA-3 group than in the EDA group (pNfL mean 7.06 pg/mL [standard deviation (SD) 2.37] vs. pNfL mean 13.04 pg/mL [SD 7.07]) (<i>p</i> &#x3c; 0.001). ROC analysis showed that pNfL predicts NEDA-3 status (sensitivity and specificity were 80.5 and 72.7%, respectively, <i>p</i> &#x3c; 0.001), and NEDA-NfL predicts NEDA-3 status (sensitivity and specificity were 97.1 and 82.9%, respectively, <i>p</i> &#x3c; 0.001). <b><i>Conclusion:</i></b> The results show that pNfL levels are a useful biomarker of disease activity determined by NEDA status in patients with MS and could be an alternative to brain magnetic resonance investigation.

scholarly journals High prevalence of intrathecal IgA synthesis in multiple sclerosis patients

2021 ◽  
Author(s):  
Ursula Muñoz ◽  
Cristina Sebal ◽  
Esther Escudero ◽  
Maria Isabel García Sánchez ◽  
Elena Urcelay ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neurological Diseases ◽  
Control Group ◽  
Control Groups ◽  
Serum Samples ◽  
Highly Sensitive ◽  
High Prevalence ◽  
Ultrasensitive Assay ◽  
Multiple Sclerosis Patients ◽  
And Control

Abstract Introduction: The detection of intrathecal IgA synthesis (IAS) in multiple sclerosis (MS) is cumbersome, for this reason, we developed a highly sensitive assay to assess it in MS. Methods: 151 MS patients and 22 controls with different neurological diseases were recruited. IgA concentration was analyzed by ELISA. Oligoclonal IgA bands to detect IAS were determined by a new ultrasensitive assay based on isoelectrofocusing (IEF). Results: Most individuals showed an IgA concentration within normal range in serum samples (95.95%) but 38.41% of individuals had a low IgA concentration in the cerebrospinal fluid (CSF), with no significant differences observed between MS and control groups, neither in CSF nor in serum. The new IEF was more sensitive than those previously described (0.01 mg/dl of IgA), and clearly identified patients with and without IAS, that was not related with IgA concentration. MS patients showed higher percentage of IAS (43.00%) than the control group (18.20) (p = 0.035), because the incidence was especially higher in MS patients with clinically isolated syndrome (CIS, 66.00%). Conclusions: Intrathecal IgA synthesis is observed more frequently in MS patients than in other neurological diseases, and with higher incidence than assumed in the past.

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