The Matrix Metalloproteinases Panel in Multiple Sclerosis Patients Treated with Natalizumab: A Possible Answer to Natalizumab Non- Responders

2018 ◽  
Vol 17 (6) ◽  
pp. 464-472 ◽  
Author(s):  
Rodica Balasa ◽  
Ciurba Bianca ◽  
Voidezan Septimiu ◽  
Simu Iunius ◽  
Hutanu Adina ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Matrix Metalloproteinases ◽  
Basal Membrane ◽  
Serum Levels ◽  
Healthy Controls ◽  
Lymphocyte Migration ◽  
Relapsing Remitting ◽  
The Matrix ◽  
Edss Score ◽  
Multiple Sclerosis Patients

Background: In the lymphocyte migration across the blood-brain barrier (BBB) in multiple sclerosis (MS), matrix metalloproteinases (MMPs) play an important role in the degradation of the basal membrane. Natalizumab (NAT), a monoclonal antibody, binds to the alpha-4 (α4) integrin leading to BBB impermeability. Approximately 30% of NAT-treated patients show clinical or MRI signs of BBB disruption. Objective: To determine whether NAT significantly influences the MMPs serum levels and to what extent these could be used as biomarkers in relapsing-remitting MS (RRMS) patients. Materials and Methods: This prospective study over a period of 8 months of NAT treatment, included 30 RRMS patients (mean age 38 ± 6 years; mean MS duration 12 ± 5 years), of which ten were initially naive to NAT and 15 were healthy controls. We determined the serum levels of the MMPs Panel (MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP12, and MMP13) quantified by a multiplex method at the beginning and end of the study. Results: After 8 months of NAT treatment, a statistically significant decrease was found in MMP9, MMP2, MMP3, MMP8, and MMP10 levels. Relapses during the study were correlated with a variation of MMP12 and MMP13 serum levels. MMP9 had the most numerous correlations with the EDSS score, Rio score, and duration of NAT treatment. MMPs signature (the sum of all MMPs) and the MMP9/MMP2 ratio significantly decreased during the study. Conclusion: 1. The serum level of MMP9 significantly decreased by NAT treatment and correlates with MS activity; 2. After eight months of NAT treatment, the MMPs signature and the MMP9/MMP2 ratio decreased; 3. MMP9 might be used as a biomarker in MS patients treated with NAT.

scholarly journals Reduced peripheral blood regulatory B cell levels are not associated with the Expanded Disability Status Scale score in multiple sclerosis

2018 ◽  
Vol 46 (9) ◽  
pp. 3970-3978 ◽  
Author(s):  
Shujun Guo ◽  
Qingqing Chen ◽  
Xiaoli Liang ◽  
Mimi Mu ◽  
Jing He ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cells ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Serum Levels ◽  
Memory B Cells ◽  
Healthy Controls ◽  
Expanded Disability Status Scale ◽  
Disability Status ◽  
Edss Score

Objective To investigate levels of regulatory B (Breg) cells, plasma cells, and memory B cells in the peripheral blood, and interleukin (IL)-10 in the serum of multiple sclerosis (MS) patients, and to determine the correlation between Breg cell levels and the Expanded Disability Status Scale (EDSS) score. Methods Levels of Breg cells, plasma cells, and memory B cells in the peripheral blood of 12 MS patients were measured using flow cytometry. IL-10 serum levels were measured by enzyme-linked immunosorbent assay. The correlation between Breg cell levels and MS EDSS score was measured using Pearson’s correlation coefficient. Results Compared with healthy controls, MS patients had decreased levels of CD19+CD24hiCD38hi Breg cells in their peripheral blood and reduced serum levels of IL-10; however, the ratios of CD19+CD27hiCD38hi plasma cells and CD19+CD27+CD24hi memory B cells to total B cells did not differ significantly between healthy controls and MS patients. CD19+CD24hiCD38hi Breg cell levels in the peripheral blood of MS patients were not significantly correlated with MS EDSS score. Conclusion Peripheral blood CD19+CD24hiCD38hi Breg cell levels and serum IL-10 levels were reduced in MS patients compared with controls, but Breg cell levels were not correlated with MS EDSS score.

CRYAB modulates the activation of CD4+ T cells from relapsing–remitting multiple sclerosis patients

2013 ◽  
Vol 19 (14) ◽  
pp. 1867-1877 ◽  
Author(s):  
Que Lan Quach ◽  
Luanne M Metz ◽  
Jenna C Thomas ◽  
Jonathan B Rothbard ◽  
Lawrence Steinman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Cytokine Production ◽  
Clinical Signs ◽  
Healthy Controls ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background: Suppression of activation of pathogenic CD4+ T cells is a potential therapeutic intervention in multiple sclerosis (MS). We previously showed that a small heat shock protein, CRYAB, reduced T cell proliferation, pro-inflammatory cytokine production and clinical signs of experimental allergic encephalomyelitis, a model of MS. Objective: We assessed whether the ability of CRYAB to reduce the activation of T cells translated to the human disease. Methods: CD4+ T cells from healthy controls and volunteers with MS were activated in vitro in the presence or absence of a CRYAB peptide (residues 73–92). Parameters of activation (proliferation rate, cytokine secretion) and tolerance (anergy, activation-induced cell death, microRNAs) were evaluated. Results: The secretion of pro-inflammatory cytokines by CD4+ T cells was decreased in the presence of CRYAB in a subset of relapsing–remitting multiple sclerosis (RRMS) participants with mild disease severity while no changes were observed in healthy controls. Further, there was a correlation for higher levels of miR181a microRNA, a marker upregulated in tolerant CD8+ T cells, in CD4+ T cells of MS patients that displayed suppressed cytokine production (responders). Conclusion: CRYAB may be capable of suppressing the activation of CD4+ T cells from a subset of RRMS patients who appear to have less disability but similar age and disease duration.

scholarly journals Monitoring cognitive change in multiple sclerosis using a computerized cognitive battery

2018 ◽  
Vol 4 (4) ◽  
pp. 205521731881551 ◽  
Author(s):  
L De Meijer ◽  
D Merlo ◽  
O Skibina ◽  
EJ Grobbee ◽  
J Gale ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Change ◽  
Progressive Multiple Sclerosis ◽  
Healthy Controls ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Serial Addition ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Cognitive Monitoring

Background Cognitive monitoring that can detect short-term change in multiple sclerosis is challenging. Computerized cognitive batteries such as the CogState Brief Battery can rapidly assess commonly affected cognitive domains. Objectives The purpose of this study was to establish the acceptability and sensitivity of the CogState Brief Battery in multiple sclerosis patients compared to controls. We compared the sensitivity of the CogState Brief Battery to that of the Paced Auditory Serial Addition Test over 12 months. Methods Demographics, Expanded Disability Status Scale scores, depression and anxiety scores were compared with CogState Brief Battery and Paced Auditory Serial Addition Test performances of 51 patients with relapsing–remitting multiple sclerosis, 19 with secondary progressive multiple sclerosis and 40 healthy controls. Longitudinal data in 37 relapsing–remitting multiple sclerosis patients were evaluated using linear mixed models. Results Both the CogState Brief Battery and the Paced Auditory Serial Addition Test discriminated between multiple sclerosis and healthy controls at baseline ( p<0.001). CogState Brief Battery tasks were more acceptable and caused less anxiety than the Paced Auditory Serial Addition Test ( p<0.001). In relapsing–remitting multiple sclerosis patients, reaction time slowed over 12 months ( p<0.001) for the CogState Brief Battery Detection (mean change –34.23 ms) and Identification (–25.31 ms) tasks. Paced Auditory Serial Addition Test scores did not change over this time. Conclusions The CogState Brief Battery is highly acceptable and better able to detect cognitive change than the Paced Auditory Serial Addition Test. The CogState Brief Battery could potentially be used as a practical cognitive monitoring tool in the multiple sclerosis clinic setting.

Development of Autoimmune Thyroid Disease in Multiple Sclerosis Patients Post-Alemtuzumab Improves Treatment Response

2020 ◽  
Vol 105 (9) ◽  
pp. e3392-e3399 ◽  
Author(s):  
Alina Sovetkina ◽  
Rans Nadir ◽  
Antonio Scalfari ◽  
Francesca Tona ◽  
Kevin Murphy ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Graves Disease ◽  
Autoimmune Thyroid ◽  
Tertiary Referral Center ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
Edss Score ◽  
Multiple Sclerosis Patients

Abstract Context Alemtuzumab is an anti-CD52 monoclonal antibody used in the treatment of relapsing-remitting multiple sclerosis (MS). Between 20% and 40% of alemtuzumab-treated MS patients develop autoimmune thyroid disease (AITD) as a side effect. Objective The objective of this work is to determine whether MS disease progression following alemtuzumab treatment differs in patients who develop AITD compared to those who do not. Design, Setting, and Patients A retrospective analysis of 126 patients with relapsing-remitting MS receiving alemtuzumab from 2012 to 2017 was conducted at a tertiary referral center. Main Outcome Measures Thyroid status, new relapses, Expanded Disability Status Scale (EDSS) score change, and disability progression following alemtuzumab were evaluated. Results Twenty-six percent (33 out of 126, 25 female, 8 male) of alemtuzumab-treated patients developed AITD, 55% of which was Graves disease. EDSS score following alemtuzumab was reduced in patients who developed AITD compared to those who did not (median [interquartile range]; AITD: –0.25 [–1 to 0.5] vs non-AITD: 0 [1-0]. P = .007]. Multivariable regression analysis confirmed that the development of AITD was independently associated with EDSS score improvement (P = .011). Moreover, AITD patients had higher relapse-free survival following alemtuzumab (P = .023). There was no difference in the number of new focal T2 lesions and contrast-enhancing magnetic resonance imaging lesions developed following alemtuzumab between the 2 groups. Conclusion Graves disease was the most common form of AITD developed by MS patients following alemtuzumab. This study suggests that MS patients who develop AITD may have an improved response to alemtuzumab, as measured by reduced disability and lower relapse rate.

Attention Network Test reveals alerting network dysfunction in multiple sclerosis

2009 ◽  
Vol 16 (1) ◽  
pp. 93-99 ◽  
Author(s):  
Carsten Urbanek ◽  
Nicholetta Weinges-Evers ◽  
Judith Bellmann-Strobl ◽  
Markus Bock ◽  
Jan Dörr ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Attention Network Test ◽  
Healthy Controls ◽  
Attention Network ◽  
Cognitive Domains ◽  
Attentional Networks ◽  
Relapsing Remitting ◽  
Cognitive Slowing ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Attention is one of the cognitive domains typically affected in multiple sclerosis. The Attention Network Test was developed to measure the function of the three distinct attentional networks, alerting, orienting, and executive control. The Attention Network Test has been performed in various neuropsychiatric conditions, but not in multiple sclerosis. Our objective was to investigate functions of attentional networks in multiple sclerosis by means of the Attention Network Test. Patients with relapsing—remitting multiple sclerosis (n = 57) and healthy controls (n = 57) matched for age, sex, and education performed the Attention Network Test. Significant differences between patients and controls were detected in the alerting network (p = 0.003), in contrast to the orienting (p = 0.696) and the conflict (p = 0.114) network of visual attention. Mean reaction time in the Attention Network Test was significantly longer in multiple sclerosis patients than in controls (p = 0.032), Multiple sclerosis patients benefited less from alerting cues for conflict resolution compared with healthy controls. The Attention Network Test revealed specific alterations of the attention network in multiple sclerosis patients which were not explained by an overall cognitive slowing.

Serum Levels of Biomarkers of Immune Activation and Associations With Neurological Impairment in Relapsing-Remitting Multiple Sclerosis Patients During Remission

2015 ◽  
Vol 18 (1) ◽  
pp. 113-119 ◽  
Author(s):  
Anna M. Witkowska ◽  
Katarzyna Socha ◽  
Jan Kochanowicz ◽  
Elżbieta Karpińska ◽  
Marta Jakoniuk ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Stem ◽  
Adhesion Molecules ◽  
Clinical Remission ◽  
Serum Levels ◽  
Neurological Impairment ◽  
Healthy Controls ◽  
Tnf Α ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

Introduction: Although much is known about cytokines and adhesion molecules during an active course of multiple sclerosis (MS), there is limited information about their serum levels during remission. Objective: This study aimed to (1) compare peripheral levels of tumor necrosis factor-α (TNF-α), soluble interleukin-2 receptor α (sIL-2Rα), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble E-selectin (sE-selectin) in MS patients during clinical remission with those of healthy controls and (2) explore possible relationships between the levels of these cytokines and adhesion molecules and neurological impairment. Methods: Initially, 92 patients with relapsing-remitting multiple sclerosis (RRMS) who were in clinical remission and 30 healthy controls were recruited for this study. The severity of neurological impairment was assessed with the Expanded Disability Status Scale (EDSS). Serum concentrations of TNF-α, sIL-2Rα, sICAM-1, and sE-selectin were determined using the sandwich enzyme-linked immunosorbent (ELISA) technique and compared between patients and controls. In a subset of RRMS patients ( n = 67), the levels of these cytokines and adhesion molecules were compared between subgroups of patients based on scores on the EDSS subscales, which measure disability level for specific neurological functions. Results: The MS patients’ TNF-α, sICAM-1, and sE-selectin levels were markedly lower than those of the controls, while their sIL-2Rα level was higher. The serum sICAM-1 concentration was positively associated with EDSS total score (ρ = .291, p = .017) as well as with the EDSS pyramidal (ρ = .267, p = .029) and cerebellar subscores (ρ = .303, p = .013). In the patients with cerebellar deficits and severe brain stem dysfunction, sICAM-1 levels were upregulated. Conclusion: Although a decreased sICAM-1 concentration was observed in RRMS patients in remission as compared to healthy controls, sICAM-1 seemed to reflect neurological impairment and clinical disability. These data suggest that increasing serum sICAM-1 levels may be associated with progression of cerebellar or brain stem perturbations. However, further studies are required to confirm these findings in a larger population of RRMS patients.

scholarly journals Phonological Fluency Strategy of Switching Differentiates Relapsing-Remitting and Secondary Progressive Multiple Sclerosis Patients

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
L. Messinis ◽  
M. H. Kosmidis ◽  
C. Vlahou ◽  
A. C. Malegiannaki ◽  
G. Gatzounis ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Verbal Fluency ◽  
Progressive Multiple Sclerosis ◽  
Word Production ◽  
Secondary Progressive Multiple Sclerosis ◽  
Healthy Controls ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients ◽  
Fluency Task

The strategies used to perform a verbal fluency task appear to be reflective of cognitive abilities necessary for successful daily functioning. In the present study, we explored potential differences in verbal fluency strategies (switching and clustering) used to maximize word production by patients with relapsing-remitting multiple sclerosis (RRMS) versus patients with secondary progressive multiple sclerosis (SPMS). We further assessed impairment rates and potential differences in the sensitivity and specificity of phonological versus semantic verbal fluency tasks in discriminating between those with a diagnosis of MS and healthy adults. We found that the overall rate of impaired verbal fluency in our MS sample was consistent with that in other studies. However, we found no differences between types of MS (SPMS, RRMS), on semantic or phonological fluency word production, or the strategies used to maximize semantic fluency. In contrast, we found that the number of switches differed significantly in the phonological fluency task between the SPMS and RRMS subtypes. The clinical utility of semantic versus phonological fluency in discriminating MS patients from healthy controls did not indicate any significant differences. Further, the strategies used to maximize performance did not differentiate MS subgroups or MS patients from healthy controls.

The Relationship Between Serum Orexin A, TGF-β, and Leptin Levels with Body Mass Index in Multiple Sclerosis Patients

2021 ◽  
Author(s):  
Sepideh Moharami ◽  
Alireza Nourazarian ◽  
Masoud Nikanfar ◽  
Delara Laghousi ◽  
behrouz shademan ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Serum Level ◽  
Serum Levels ◽  
Healthy Controls ◽  
Control Groups ◽  
Orexin A ◽  
The Mean ◽  
Multiple Sclerosis Patients ◽  
And Control ◽  
The Relationship

Abstract Backgrounds: Multiple Sclerosis (MS) is a chronic inflammatory and autoimmune disease linked to several inflammatory and dietary parameters. This study was carried out to determine the relationship between serum leptin, orexin-A, and TGF-β levels with BMI in MS patients.Methods and results: In this cross-sectional study, 25 relapsing-remitting multiple sclerosis (RRMS) patients and 40 healthy controls were enrolled. The serum level of Leptin, Orexin-A, and TGF- were measured by the Enzyme-linked immunosorbent assay (ELISA). The data was analyzed using descriptive statistics, t-test, Chi-square test, and Linear regression test. A total of 65 volunteers, including 25 MS patients and 40 healthy, were enrolled in the study. The mean age of individuals in the case and control groups was 38.04 ± 7.53 and 40.23 ± 5.88. There were no statistically significant differences between the case and control groups regarding gender, age, alcohol, and cigarette use (P>0.05). The mean serum levels of Orexin-A and TGF-ß were lower among multiple sclerosis patients than in healthy controls, but leptin was higher (42.8 vs. 18.9 ng/ml, P<0.001). The relationship between BMI and serum levels of Orexin-A, TGF-ß, and Leptin among Multiple Sclerosis patients was not statistically significant (P > 0.05).Conclusion: Our results showed that the serum levels of Orexin-A and TGF-β were significantly lower. The serum level of leptin was higher among multiple sclerosis patients than among healthy controls. Also, there was no statistically significant relationship between BMI and serum levels of Orexin-A, TGF-ß, and Leptin among multiple sclerosis patients.

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