scholarly journals CCN3 is dynamically regulated by treatment and disease state in multiple sclerosis

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Michelle Naughton ◽  
Jill Moffat ◽  
George Eleftheriadis ◽  
Nira de la Vega Gallardo ◽  
Andrew Young ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease State ◽  
Immune Mediated ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Patient Groups ◽  
Ccn3 Expression ◽  
Disease Modifying Treatment ◽  
And Control

Abstract Background Multiple sclerosis (MS) is an immune-mediated disease that damages myelin in the central nervous system (CNS). We investigated the profile of CCN3, a known regulator of immune function and a potential mediator of myelin regeneration, in multiple sclerosis in the context of disease state and disease-modifying treatment. Methods CCN3 expression was analysed in plasma, immune cells, CSF and brain tissue of MS patient groups and control subjects by ELISA, western blot, qPCR, histology and in situ hybridization. Results Plasma CCN3 levels were comparable between collective MS cohorts and controls but were significantly higher in progressive versus relapsing-remitting MS and between patients on interferon-β versus natalizumab. Higher body mass index was associated with higher CCN3 levels in controls as reported previously, but this correlation was absent in MS patients. A significant positive correlation was found between CCN3 levels in matched plasma and CSF of MS patients which was absent in a comparator group of idiopathic intracranial hypertension patients. PBMCs and CD4+ T cells significantly upregulated CCN3 mRNA in MS patients versus controls. In the CNS, CCN3 was detected in neurons, astrocytes and blood vessels. Although overall levels of area immunoreactivity were comparable between non-affected, demyelinated and remyelinated tissue, the profile of expression varied dramatically. Conclusions This investigation provides the first comprehensive profile of CCN3 expression in MS and provides rationale to determine if CCN3 contributes to neuroimmunological functions in the CNS.

A case of immune-mediated encephalitis related to daclizumab therapy

2018 ◽  
Vol 25 (5) ◽  
pp. 750-753 ◽  
Author(s):  
Michael Devlin ◽  
Andrew Swayne ◽  
Martin Newman ◽  
Cullen O’Gorman ◽  
Helen Brown ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Reactions ◽  
Brain Biopsy ◽  
Disease Modifying Therapy ◽  
Immune Mediated ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Disease Modifying ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Csf Examination

This report will detail a case of immune-mediated encephalitis in the context of daclizumab therapy. Daclizumab is a humanised monoclonal antibody which, prior to its recent worldwide withdrawal due to safety concerns, was utilised as a disease-modifying therapy in relapsing-remitting multiple sclerosis. The withdrawal of this therapy was prompted by concerns over 12 cases of serious immune-mediated adverse reactions in the central nervous system. We report an additional case, including clinical data and results of neuroimaging, cerebrospinal fluid (CSF) examination and brain biopsy.

scholarly journals Clinical and epidemiological profile of patients with multiple sclerosis in Uberaba, Minas Gerais, Brazil

2011 ◽  
Vol 69 (2a) ◽  
pp. 184-187 ◽  
Author(s):  
Sônia Beatriz Félix Ribeiro ◽  
Danilo Fonseca Maia ◽  
João Batista Ribeiro ◽  
Fabrízio Antônio Gomide Cardoso ◽  
Cátia Silva
Keyword(s):  
Multiple Sclerosis ◽  
College Education ◽  
Average Score ◽  
Initial Symptom ◽  
Immune Mediated ◽  
Disability Status ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Epidemiological Profile ◽  
Brazilian Studies

Multiple sclerosis (MS) is an immune-mediated disease that affects the central nervous system. Clinical presentation and prevalence vary widely around the world. OBJECTIVE: To describe the clinical and epidemiological aspects of patients with MS in Uberaba (MG). METHOD: We conducted a transversal descriptive study, with data analysis of 35 patients with MS. RESULTS: Prevalence of MS was 12.5 cases/100,000 inhabitants, with a predominance in females (71.4%) and Caucasoid (85.7%). The current average age was (43.8 ys). The most common initial symptom was sensory (40%), followed by optical neuritis (25.7%). Expanded Disability Status Scale average score was 2.4. The relapsing-remitting form was predominant (88.6%), most (74.3%) were on immunomodulatory treatment and (40%) had college education. CONCLUSION: Prevalence of MS in Uberaba (MG) is considered average in accordance to Kurtzke and Page and clinical features are consistent with most Brazilian studies.

High Dose Cyclophosphamide for Moderate to Severe Refractory Multiple Sclerosis: 2-Year Follow-up (investigational new drug No. 65863).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4744-4744
Author(s):  
Douglas Gladstone
Keyword(s):  
Multiple Sclerosis ◽  
Brain Magnetic Resonance Imaging ◽  
High Dose ◽  
Immune Mediated ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Immune Manipulation ◽  
Edss Score ◽  
Disease Modifying Agents

Abstract Abstract 4744 Background High dose cyclophosphamide (HDC) is a chemotherapy treatment designed to eradicate autoreative B- and T-cells responsible for lymphocyte-mediated autoimmune illness, while sparing the pluripotent blood stem cell of any ill effects. Multiple sclerosis (MS) is the most common inflammatory and demyelinating immune-mediated disorder of the central nervous system in young adults. Methods Patients with moderate to severe, refractory MS, defined as an Expanded Disability Status Scale (EDSS) score of 3.5 or higher after 2 or more Food and Drug Administration-approved disease-modifying agents, received 200 mg/kg of cyclophosphamide over 4 days. For the following 2 years, quarterly EDSS score evaluations and biannual brain magnetic resonance imaging and neuro-ophthalmologic evaluations were obtained. Results 15 patients were evaluated for clinical response. During follow-up, no patients increased their baseline EDSS score by more than 1.0. EDSS score stability or decrease was realized in 5 of 7 (71%) patients with relapsing remitting MS and 5 of 8 (62%) patients with secondary progressive MS patients. 4 patients required additional immunomodulatory treatment after treatment. Neurologic improvement involved changes in gait, bladder control, and visual function. Treatment response was seen regardless of the baseline presence or absence of contrast lesion activity. Conclusions HDC can effectively decrease symptoms, stop disease progression, and allow for disability regression in RR and SPMS patients. The most appropriate candidates for HDC, its duration of benefit and the potential need for prophylactic preventative immune manipulation after HDC all require further investigation. Disclosures: Off Label Use: cyclophosphamide: IND# 65863.

scholarly journals Macrophage Plasticity and Polarization Are Altered in the Experimental Model of Multiple Sclerosis

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 837
Author(s):  
Alessandro Leuti ◽  
Emanuela Talamonti ◽  
Antonietta Gentile ◽  
Marta Tiberi ◽  
Alessandro Matteocci ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Demyelinating Disease ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Phenotypic Alteration ◽  
Immune Mediated ◽  
Polychromatic Flow Cytometry ◽  
The Central Nervous System ◽  
And Control ◽  
M1 And M2 Macrophages

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. MS is characterized by infiltrations of leukocytes such as T and B lymphocytes and macrophages. Macrophages have been identified as major effectors of inflammation and demyelination in both MS and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the activation and heterogeneity of macrophages in MS has been poorly investigated. Thus, in this study, we evaluated M1 and M2 macrophages immunophenotype from EAE and control mice by analyzing over 30 surface and intracellular markers through polychromatic flow cytometry, qRT-PCR, and ELISA assay. We showed that M1 macrophages possessed a higher proinflammatory profile in EAE compared to control mice, since they expressed higher levels of activation/co-stimulatory markers (iNOS, CD40, and CD80) and cytokines/chemokines (IL-6, IL-12, CCL2, and CXCL10), whereas M2 lost their M2-like phenotype by showing a decreased expression of their signature markers CD206 and CCL22, as well as a concomitant upregulation of several M1 makers. Furthermore, immunization of M1 and M2 macrophages with MOG35-55 led to a significant hyperactivation of M1 and a concomitant shift of anti-inflammatory M2 to pro-inflammatory M1 macrophages. Overall, we provide evidence for a phenotypic alteration of M1/M2 balance during MS, which can be of crucial importance not only for a better understanding of the immunopathology of this neurodegenerative disease but also to potentially develop new macrophage-centered therapeutic strategies.

scholarly journals Increased Expression of Ephrins on Immune Cells of Patients with Relapsing Remitting Multiple Sclerosis Affects Oligodendrocyte Differentiation

2021 ◽  
Vol 22 (4) ◽  
pp. 2182
Author(s):  
Maya Golan ◽  
Avivit Krivitsky ◽  
Karin Mausner-Fainberg ◽  
Moshe Benhamou ◽  
Ifat Vigiser ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cells ◽  
Inhibitory Effect ◽  
Autoimmune Response ◽  
Immune Mediated ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

The effect of the inflammatory response on regenerative processes in the brain is complex. This complexity is even greater when the cause of the tissue damage is an autoimmune response. Multiple sclerosis (MS) is an immune-mediated disease in which demyelination foci are formed in the central nervous system. The degree of repair through oligodendrocyte regeneration and remyelination is insufficient. Ephrins are membrane-bound ligands activating tyrosine kinase signaling proteins that are known to have an inhibitory effect on oligodendrocyte regeneration. In this study, we examined the expression of ephrins on immune cells of 43 patients with relapsing-remitting (RR) MS compared to 27 matched healthy controls (HC). We found an increased expression of ephrin-A2, -A3 and -B3, especially on T cell subpopulations. We also showed overexpression of ephrins on immune cells of patients with RR-MS that increases the forward signaling pathway and that expression of ephrins on immune cells has an inhibitory effect on the differentiation of oligodendrocyte precursor cells (OPCs) in vitro. Our study findings support the concept that the immune activity of T cells in patients with RR-MS has an inhibitory effect on the differentiation capacity of OPCs through the expression and forward signaling of ephrins.

Elevated urinary excretion of aluminium and iron in multiple sclerosis

2006 ◽  
Vol 12 (5) ◽  
pp. 533-540 ◽  
Author(s):  
Christopher Exley ◽  
Godwin Mamutse ◽  
Olga Korchazhkina ◽  
Eleanor Pye ◽  
Stanislav Strekopytov ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Urinary Excretion ◽  
Demyelinating Disease ◽  
Therapeutic Option ◽  
Analytical Techniques ◽  
Potential Marker ◽  
Immune Mediated ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Environmental Toxin

Multiple sclerosis (MS) is a chronic, immune-mediated, demyelinating disease of the central nervous system of as yet unknown aetiology. A consensus of opinion has suggested that the disorder is the result of an interplay between environmental factors and susceptibility genes. We have used a battery of analytical techniques to determine if the urinary excretion of i) markers of oxidative damage; ii) iron and iii) the environmental toxin aluminium and its antagonist, silicon, are altered in relapsing remitting (RRMS) and secondary progressive MS (SPMS). Urinary concentrations of oxidative biomarkers, MDA and TBARS, were not found to be useful indicators of inflammatory disease in MS. However, urinary concentrations of another potential marker for inflammation and oxidative stress, iron, were significantly increased in SPMS ( P<0.01) and insignificantly increased in RRMS ( P>0.05). Urinary concentrations of aluminium were also significantly increased in RRMS ( P<0.001) and SPMS ( P<0.05) such that the levels of aluminium excretion in the former were similar to those observed in individuals undergoing metal chelation therapy. The excretion of silicon was lower in MS and significantly so in SPMS ( P<0.05). Increased excretion of iron in urine supported a role for iron dysmetabolism in MS. Levels of urinary aluminium excretion similar to those seen in aluminium intoxication suggested that aluminium may be a hitherto unrecognized environmental factor associated with the aetiology of MS. If aluminium is involved in MS then an increased dietary intake of its natural antagonist, silicon, might be a therapeutic option.

Case Report: Delayed Alemtuzumab-Induced Concurrent Neutropenia and Thrombocytopenia in Relapsing-Remitting Multiple Sclerosis

2021 ◽  
pp. 089719002110212
Author(s):  
Akaansha Ganju ◽  
James C. Stock ◽  
Kim Jordan
Keyword(s):  
Multiple Sclerosis ◽  
Case Reports ◽  
Severe Neutropenia ◽  
Cell Counts ◽  
Immune Mediated ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Study Participants ◽  
Relapsing Remitting Multiple Sclerosis

Alemtuzumab is an anti-CD52 monoclonal antibody used to treat relapsing-remitting multiple sclerosis following failure of second-line medications. It is administered intravenously in 2 treatment sequences 1 year apart. This drug is frequently associated with mild infusion reactions within days of administration, increased infection risk, and long term adverse events from secondary autoimmunity. Alemtuzumab-induced serious immune-mediated thrombocytopenia (ITP) is well-reported and occurred in 1.0-2.2% of participants in initial phase 2 and 3 trials for multiple sclerosis. Significant neutropenia, however, is rare and was only observed in 0.1% of study participants. Delayed neutropenia and/or ITP is thought to occur from secondary autoimmunity. Few case reports have described severe neutropenia occurring beyond 2 months of last alemtuzumab dose. We present an unusual case of delayed combined neutropenia and thrombocytopenia that occurred 15 months after the second infusion of alemtuzumab. The patient was asymptomatic and presented following discovery of neutropenia and thrombocytopenia during routine laboratory studies. The patient responded to steroids initially and was discharged, although outpatient cell counts subsequently revealed recurrent neutropenia and ITP. The adverse drug reaction probability (Naranjo) scale was completed and showed probable likelihood that the adverse event was alemtuzumab-related. Long term screening for delayed hematologic abnormalities, at least 4 years after initial dose, is necessary when using alemtuzumab. Greater research is needed to understand the mechanism of drug-associated neutropenia.

scholarly journals HIV infection and multiple sclerosis: a case with unexpected “no evidence of disease activity” status

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199957
Author(s):  
Fernando Labella ◽  
Fernando Acebrón ◽  
María del Carmen Blanco-Valero ◽  
Alba Rodrígez-Martín ◽  
Ángela Monterde Ortega ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Hiv Infection ◽  
Disease Activity ◽  
Demyelinating Disease ◽  
Clinical Course ◽  
Disease Modifying Drugs ◽  
Immunodeficiency Virus ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Disease Modifying

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system whose etiology remains unclear. It has been suggested that MS can be triggered by certain viruses; however, human immunodeficiency virus (HIV) infection is associated with reduced incidence of MS. We present the case of a young patient diagnosed with active relapsing-remitting MS whose clinical course substantially improved following HIV infection and treatment. The patient achieved no evidence of disease activity status without any disease-modifying drugs. Both HIV-induced immunosuppression and antiretroviral therapy may have attenuated the clinical course in this patient.

scholarly journals Evaluation the FLAIR Sensitivity and DWI Post-inject in Comparison with Delayed Enhancement T1w for Better Detection of Active MS Lesions

2018 ◽  
Author(s):  
M Hoseinipourasl ◽  
M Zandkarimi ◽  
J Abdolmohammadi ◽  
K Sharifi ◽  
S Miraki
Keyword(s):  
Multiple Sclerosis ◽  
Genetic Factors ◽  
Vision Loss ◽  
Blurred Vision ◽  
Secondary Progressive ◽  
Signal Suppression ◽  
Relapsing Remitting ◽  
Loss Of Balance ◽  
The Central Nervous System ◽  
With Memory

Background: Multiple sclerosis (MS) is a chronic, typically progressive and most common autoimmune disease which damaged the central nervous system. According to the reports in 2008, this disorder has affected 2 and 2.5 million people globally. While the reason is not clear, proposed causes for this include immunologic, environmental, infectious and genetic factors, and sexuality. MS can cause many symptoms, including blurred vision, loss of balance, poor coordination, slurred speech, tremors, numbness, extreme fatigue, problems with memory and concentration, paralysis, blindness, and more. There are four distinguished illness fields in MS: relapsing-remitting MS (RRMS), primary–progressive MS (PPMS), secondary–progressive MS (SPMS), and progressive–relapsing. MRI is a great tool to identify the asymptomatic distribution of lesions in space and time.Materials and Methods: 32 patients with MS plaques were evaluated by FLAIR and DWI pre- and post-Gadolinium injection compared with 15minutes delay T1w SE.Results: FLAIR post-inject had significantly better detection of the number and signal intensity of active MS lesions. DWI and ADC images detected active plaques different from non-active lesions without contrast.Conclusion: The result of this study showed that FLAIR post-inject had the highest sensitivity in detection of active MS lesions due to the CSF signal suppression in FLAIR, thus offering enough TR time recovery in active enhanced plaques.

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