Multiple sclerosis immunology: The healthy immune system vs the MS immune system

Neurology ◽  
2009 ◽  
Vol 74 (Issue 1, Supplement 1) ◽  
pp. S2-S8 ◽  
Author(s):  
L. H. Kasper ◽  
J. Shoemaker
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Healthy Immune System

scholarly journals Infectious and Noninfectious Granulomatosis in Patient with Multiple Sclerosis: Diagnostic Dilemmas and Followup

2014 ◽  
Vol 2014 ◽  
pp. 1-6
Author(s):  
Jelena Paovic ◽  
Predrag Paovic ◽  
Vojislav Sredovic
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Pulmonary Tuberculosis ◽  
Cataract Surgery ◽  
Systemic Infection ◽  
Neurological Manifestations ◽  
Initial Attack ◽  
Mri Findings ◽  
Retrobulbar Neuritis ◽  
Preoperative Procedures

Patient was followed up over the course of 30 years. In 1978, after severe systemic infection followed by fever, pulmonary edema, and numerous neurological manifestations, patient was differentially diagnosed with apoplectic form of multiple sclerosis (MS), which was confirmed a year later via neurological and MRI findings. Approximately 20 years following the initial attack, sarcoidosis was diagnosed during the regular preoperative procedures required for cataract surgery. As consequence of lower immune system, infectious granulomatosis in form of pulmonary tuberculosis developed. Ophthalmological findings revealed bilateral retrobulbar neuritis (RBN) approximately six years after initial attack. This developed into total uveitis with retinal periphlebitis and anterior granulomatous uveitis—all of which are clinically similar in both MS and sarcoidosis.

Vaccination opportunities in multiple sclerosis patients treated with cladribine tablets

2021 ◽  
Vol 20 ◽  
Author(s):  
Lucia Moiola ◽  
Agostino Riva ◽  
Ferdinando Nicoletti ◽  
Antonio Uccelli ◽  
Marco Salvetti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Mechanism Of Action ◽  
Vaccination Campaign ◽  
Humoral Response ◽  
Focused Attention ◽  
Vulnerable Patients ◽  
Mass Vaccination Campaign ◽  
Multiple Sclerosis Patients ◽  
Vaccination Campaigns

: The COVID-19 pandemic and the mass vaccination campaign highlighted the situation of the most vulnerable patients. In this work, we focused attention on patients who have Multiple Sclerosis (MS), particularly in treatment with cladribine tablets, trying to understand if and when it is possible to administer the vaccine successfully. Considering the innovative topic, we reviewed the existing literature with an analysis of the experiences also related to other vaccinations, including influenza and VZV, and very recent data from countries with vaccination campaigns already advanced. Overall, we have taken into account the mechanism of action, the pharmacokinetic/pharmacodynamic of cladribine and the changes in the immune system after its administration, together with the preliminary data about the humoral response to influenza, VZV and SARS-CoV-2 vaccinations in cladribine treated patients. In conclusion, data showed that the use of cladribine tablets seems to permit flexibility regarding vaccination timing and we suggest that vaccination in those patients should be safe and effective.

scholarly journals Suppression of the Peripheral Immune System Limits the Central Immune Response Following Cuprizone-Feeding: Relevance to Modelling Multiple Sclerosis

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1314 ◽  
Author(s):  
Sen ◽  
Almuslehi ◽  
Gyengesi ◽  
Myers ◽  
Shortland ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Immune System ◽  
Adaptive Immune System ◽  
Synaptic Function ◽  
Adaptive Immune ◽  
Splenic Atrophy ◽  
The Impact ◽  
The Brain ◽  
Inside Out

Cuprizone (CPZ) preferentially affects oligodendrocytes (OLG), resulting in demyelination. To investigate whether central oligodendrocytosis and gliosis triggered an adaptive immune response, the impact of combining a standard (0.2%) or low (0.1%) dose of ingested CPZ with disruption of the blood brain barrier (BBB), using pertussis toxin (PT), was assessed in mice. 0.2% CPZ(±PT) for 5 weeks produced oligodendrocytosis, demyelination and gliosis plus marked splenic atrophy (37%) and reduced levels of CD4 (44%) and CD8 (61%). Conversely, 0.1% CPZ(±PT) produced a similar oligodendrocytosis, demyelination and gliosis but a smaller reduction in splenic CD4 (11%) and CD8 (14%) levels and no splenic atrophy. Long-term feeding of 0.1% CPZ(±PT) for 12 weeks produced similar reductions in CD4 (27%) and CD8 (43%), as well as splenic atrophy (33%), as seen with 0.2% CPZ(±PT) for 5 weeks. Collectively, these results suggest that 0.1% CPZ for 5 weeks may be a more promising model to study the ‘inside-out’ theory of Multiple Sclerosis (MS). However, neither CD4 nor CD8 were detected in the brain in CPZ±PT groups, indicating that CPZ-mediated suppression of peripheral immune organs is a major impediment to studying the ‘inside-out’ role of the adaptive immune system in this model over long time periods. Notably, CPZ(±PT)-feeding induced changes in the brain proteome related to the suppression of immune function, cellular metabolism, synaptic function and cellular structure/organization, indicating that demyelinating conditions, such as MS, can be initiated in the absence of adaptive immune system involvement.

scholarly journals Does Resetting the Immune System Fix Multiple Sclerosis?

2019 ◽  
Vol 47 (1) ◽  
pp. 1-10
Author(s):  
Gauruv Bose ◽  
Simon D. X. Thebault ◽  
Harold L. Atkins ◽  
Mark S. Freedman
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Therapeutic Option ◽  
Disease Course ◽  
Phase Ii Trials ◽  
Durable Response ◽  
Treatment Protocols ◽  
Hematopoietic Stem ◽  
Aggressive Disease ◽  
Conditioning Regimens

Abstract:Multiple sclerosis is the leading non-traumatic cause of disability in young adults, affecting up to 100,000 Canadians. This chronic inflammatory and neurodegenerative disease of the central nervous system leads to irreversible neurologic disability if inadequately controlled. Though many current medications are available that reduce inflammatory damage, most patients continue to show some evidence of disease activity and accrue disability. In this review, we discuss the role of immune ablation followed by autologous hematopoietic stem cell transplantation (AHSCT), a therapeutic option for select patients with a more aggressive disease course. By “resetting” the immune system with a variety of ablative conditioning regimens, followed by immune reconstitution, this therapy has shown a durable response in halting evidence of inflammatory activity in most patients, without the need for continued disease-modifying therapies (DMT). Since the introduction of this therapy, there have been advances in patient selection and supportive care, such that morbidity has significantly declined and treatment-related mortality is minimized. Recent phase-II trials have shown excellent results in efficacy and safety of AHSCT; however, challenges exist which require ongoing study. The future challenges include comparing the variety of AHSCT conditioning regimens with each other as well as with existing highly effective DMT; identifying patients with an aggressive disease course through novel biomarkers who may benefit the most from AHSCT; and surveillance of long-term outcomes of different treatment protocols. In select patients, replacing the immune system with AHSCT holds promise of fundamentally altering the trajectory of their aggressive disease course.

scholarly journals The Potential of Computational Modeling to Predict Disease Course and Treatment Response in Patients with Relapsing Multiple Sclerosis

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 586 ◽  
Author(s):  
Francesco Pappalardo ◽  
Giulia Russo ◽  
Marzio Pennisi ◽  
Giuseppe Alessandro Parasiliti Palumbo ◽  
Giuseppe Sgroi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Computational Modeling ◽  
Response To Treatment ◽  
Oligoclonal Bands ◽  
Host Immune System ◽  
Immunological Parameters ◽  
Disease Modifying Drugs ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Multiple Sclerosis

As of today, 20 disease-modifying drugs (DMDs) have been approved for the treatment of relapsing multiple sclerosis (MS) and, based on their efficacy, they can be grouped into moderate-efficacy DMDs and high-efficacy DMDs. The choice of the drug mostly relies on the judgment and experience of neurologists and the evaluation of the therapeutic response can only be obtained by monitoring the clinical and magnetic resonance imaging (MRI) status during follow up. In an era where therapies are focused on personalization, this study aims to develop a modeling infrastructure to predict the evolution of relapsing MS and the response to treatments. We built a computational modeling infrastructure named Universal Immune System Simulator (UISS), which can simulate the main features and dynamics of the immune system activities. We extended UISS to simulate all the underlying MS pathogenesis and its interaction with the host immune system. This simulator is a multi-scale, multi-organ, agent-based simulator with an attached module capable of simulating the dynamics of specific biological pathways at the molecular level. We simulated six MS patients with different relapsing–remitting courses. These patients were characterized based on their age, sex, presence of oligoclonal bands, therapy, and MRI lesion load at the onset. The simulator framework is made freely available and can be used following the links provided in the availability section. Even though the model can be further personalized employing immunological parameters and genetic information, we generated a few simulation scenarios for each patient based on the available data. Among these simulations, it was possible to find the scenarios that realistically matched the real clinical and MRI history. Moreover, for two patients, the simulator anticipated the timing of subsequent relapses, which occurred, suggesting that UISS may have the potential to assist MS specialists in predicting the course of the disease and the response to treatment.

scholarly journals The Risk Factors for Immune System Impairment and the Need for Lifestyle Changes

2020 ◽  
Vol 8 (01) ◽  
pp. 025-028
Author(s):  
Gunjan Y. Trivedi ◽  
Banshi Saboo
Keyword(s):  
Infectious Disease ◽  
Risk Factors ◽  
Immune System ◽  
Chronic Disease ◽  
Lifestyle Changes ◽  
Complex Nature ◽  
Lifestyle Choices ◽  
System Risk ◽  
Healthy Immune System

AbstractHealthy immune system helps in enhancing the quality of life and reduces the risk of infectious disease. Chronic disease increases the risk of immune system impairment. The article reviews the evidence on risk factors causing immune system imbalance and articulates the complex nature of the relationships between immune system risk factors, chronic disease, and infectious disease to highlight the importance of lifestyle choices. Finally, some evidence is presented on mind–body interventions and lifestyle choices for enhancing the immune system function.

scholarly journals Free Light Chains as a Novel Diagnostic Biomarker of Immune System Abnormalities in Multiple Sclerosis and HIV Infection

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Monika Gudowska-Sawczuk ◽  
Barbara Mroczko
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Hiv Infection ◽  
Light Chains ◽  
Laboratory Diagnostics ◽  
Elevated Concentration ◽  
Free Light Chains ◽  
Heavy Chains ◽  
Immune System Dysfunction ◽  
Pubmed Database

Introduction. Immunoglobulins are molecules composed of two heavy and two light chains. Light chains are produced by B lymphocytes during the synthesis of immunoglobulins, and physiologically light chains are generally produced in excess compared to heavy chains. Light chains that are not combined to heavy chains in a whole immunoglobulin are called free light chains (FLCs). B-cell abnormalities are associated with disorders leading to an abnormal concentration of free light chains. In this study, we focus on the described changes of serum and cerebrospinal fluid concentration of free light chains in inflammatory disorders: multiple sclerosis, HIV infection, and HIV-associated lymphomas. Methods. We performed broad research of the literature pertaining to our investigation via the MEDLINE/PubMed database. Results. It has been proven that FLC determination can provide rapid information about intrathecal inflammation in patients with multiple sclerosis. Moreover, literature data suggest that free light chain determination is the most interesting alternative for oligoclonal band analysis. In the present review, we also described that HIV-related immune system dysfunction is associated with an elevated concentration of serum-free light chains. Additionally, FLCs are potentially a strong and sensitive predictor of the risk of developing HIV-associated lymphomas. Conclusion. Based on these published findings, we suggest that free light chains have high diagnostic sensitivity, which probably enables application in laboratory diagnostics.

scholarly journals The FLUENT study design: investigating immune cell subset and neurofilament changes in patients with relapsing multiple sclerosis treated with fingolimod

2019 ◽  
Vol 5 (1) ◽  
pp. 205521731881924 ◽  
Author(s):  
Jeffrey A Cohen ◽  
Amit Bar-Or ◽  
Bruce A C Cree ◽  
Yang Mao-Draayer ◽  
May H Han ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Immune Cell ◽  
Cell Subset ◽  
Adaptive Immune System ◽  
Study Cohort ◽  
Open Label ◽  
Receptor Modulator ◽  
Circulating Lymphocytes ◽  
B Cell Subsets

Background Fingolimod is a sphingosine 1-phosphate receptor modulator for the treatment of patients with relapsing forms of multiple sclerosis (RMS). Fingolimod sequesters lymphocytes within lymphoid tissue thereby reducing the counts of circulating lymphocytes. However, fingolimod’s effects on the innate and adaptive components of the immune system are incompletely understood. Objective The FLUENT study will investigate temporal changes in circulating immune cell subsets in patients with RMS treated with fingolimod. Secondary objectives include examining the association between anti-John Cunningham virus (JCV) antibody status/index and phenotypic changes in innate and T and B cell subsets in patients on fingolimod therapy, and the association between serum neurofilament levels and clinical outcomes. Methods FLUENT is a prospective, multicenter, two-cohort, nonrandomized, open-label Phase IV study. Cohort 1 will include fingolimod-naïve patients and Cohort 2 will include patients who have received fingolimod 0.5 mg/day continuously for ≥2 years. Changes in the cellular components of the innate and adaptive immune system will be characterized over 12 months. Results The study is ongoing. Conclusion FLUENT may provide evidence for the use of immunologic profiling in predicting efficacy and risk of infection in patients with RMS treated with fingolimod.

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