Multiple sclerosis and faecal microbiome transplantation: are you going to eat that?

2019 ◽  
Vol 10 (1) ◽  
pp. 27-32 ◽  
Author(s):  
A.C. Wing ◽  
M. Kremenchutzky
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Current Knowledge ◽  
Clinical Trial Design ◽  
Host Immune System ◽  
Immune Mediated ◽  
Clinical Benefits ◽  
Multiple Sclerosis Patients ◽  
Faecal Microbiome ◽  
Vitamin Production

Gut microbiome interaction goes beyond commensal function as vitamin production or support nutrients digestion. It also interplays with the host immune system and may be related to the development of immune-mediated diseases. Multiple sclerosis patients have dysbiosis compared to healthy individuals. But how this relates to disease development and severity is still uncertain. Dietary change including probiotic mixtures or ketogenic regimen has proven to change microbiome in multiple sclerosis (MS) subjects to one similar to healthy controls. However, proof of clinical benefits is lacking. We dissert on current knowledge about immune system and gut bacteria interactions. We discuss faecal microbial transplantation as a potential intervention to ameliorate gut dysbiosis in MS as well as the caveats of a clinical trial design.

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 Mutual Interplay of Host Immune System and Gut Microbiota in the Immunopathology of Atherosclerosis

2020 ◽  
Vol 21 (22) ◽  
pp. 8729 ◽  
Author(s):  
Chih-Fan Yeh ◽  
Ying-Hsien Chen ◽  
Sheng-Fu Liu ◽  
Hsien-Li Kao ◽  
Ming-Shiang Wu ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Cytokine Production ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Inflammasome Activation ◽  
Host Immune System ◽  
Gut Permeability ◽  
And Function ◽  
Progression Of Atherosclerosis

Inflammation is the key for the initiation and progression of atherosclerosis. Accumulating evidence has revealed that an altered gut microbiome (dysbiosis) triggers both local and systemic inflammation to cause chronic inflammatory diseases, including atherosclerosis. There have been some microbiome-relevant pro-inflammatory mechanisms proposed to link the relationships between dysbiosis and atherosclerosis such as gut permeability disruption, trigger of innate immunity from lipopolysaccharide (LPS), and generation of proatherogenic metabolites, such as trimethylamine N-oxide (TMAO). Meanwhile, immune responses, such as inflammasome activation and cytokine production, could reshape both composition and function of the microbiota. In fact, the immune system delicately modulates the interplay between microbiota and atherogenesis. Recent clinical trials have suggested the potential of immunomodulation as a treatment strategy of atherosclerosis. Here in this review, we present current knowledge regarding to the roles of microbiota in contributing atherosclerotic pathogenesis and highlight translational perspectives by discussing the mutual interplay between microbiota and immune system on atherogenesis.

Moving Immune Therapy Forward Targeting TME

2020 ◽  
Author(s):  
Kayla F Goliwas ◽  
Jessy S. Deshane ◽  
Craig A Elmets ◽  
Mohammad Athar
Keyword(s):  
Immune System ◽  
Targeted Therapies ◽  
Immune Therapy ◽  
Clinical Trial Design ◽  
Therapeutic Interventions ◽  
Host Immune System ◽  
Host Immune Responses ◽  
Metabolic Plasticity ◽  
Cancer Pathogenesis ◽  
Immune Therapies

The host immune system shapes the fate of tumor progression. Hence, manipulating patients' immune system to activate host immune responses against cancer pathogenesis is a promising strategy to develop effective therapeutic interventions for metastatic and drug resistant cancers. Understanding the dynamic mechanisms within the tumor microenvironment (TME) that contribute to heterogeneity and metabolic plasticity is essential to enhance the patients' responsiveness to immune targeted therapies. Riera-Domingo et. al. describe the immune landscape within the TME, and highlight the significance of metabolic and hypoxic signatures that impact immune function and response to immunotherapy. Current literature in this field confirms that targeting tumor metabolism and the acidic microenvironment commonly associated with tumors may present as viable strategies to modulate the host immune system in favor of developing highly effective immune targeted therapies. However, development of better tools to understand tumor-immune interactions and identify mechanisms driving non-responders, more innovative clinical trial design, and new therapies will need to be identified to move the field forward. Personalized immune therapies incorporating metabolic and microbiome-based gene signatures to influence the therapeutic response and novel methods to generate immunologically "hot" tumors are at the forefront of immunotherapy currently. The combination of these approaches with clinically approved immunotherapies will also be valuable moving forward.

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 COVID-19 in patients with multiple sclerosis undergoing disease-modifying treatments

2020 ◽  
pp. 135245852097181
Author(s):  
Alice Laroni ◽  
Irene Schiavetti ◽  
Maria Pia Sormani ◽  
Antonio Uccelli
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Immunosuppressive Drugs ◽  
Data Sets ◽  
Immune Mediated ◽  
Disease Modifying ◽  
Human Coronaviruses ◽  
Clinical Pictures ◽  
Available Information

The CoronaVirus Disease 19 (COVID-19) pandemic is a threat of particular concern for people affected by chronic immune-mediated diseases, such as multiple sclerosis (MS), who are often treated with immunomodulatory and immunosuppressive drugs, which may increase the risk of infections in general. At the beginning of the COVID-19 pandemic, empirical guidelines on how to manage treatments for immune-mediated diseases, including MS, were released. Subsequently, the first clinical pictures and data sets have been published, describing the outcomes of COVID-19 in patients with MS treated with immunomodulatory and immunosuppressive drugs. Here we will review available information on how infections by human coronaviruses affect the immune system in untreated subjects and in patients affected by MS treated with drugs which modulate the immune system.

Failure of allogeneic bone marrow transplantation to arrest disease activity in multiple sclerosis

2007 ◽  
Vol 13 (8) ◽  
pp. 1071-1075 ◽  
Author(s):  
D.R. Jeffery
Keyword(s):  
Multiple Sclerosis ◽  
Bone Marrow ◽  
Immune System ◽  
Bone Marrow Transplantation ◽  
Autoimmune Disease ◽  
Disease Activity ◽  
Marrow Transplantation ◽  
Myelogenous Leukemia ◽  
Allogeneic Bone ◽  
Immune Mediated

Multiple sclerosis (MS) is thought to be an autoimmune disease in which activated T-cells initiate a macrophage mediated destruction of CNS myelin. Bone marrow transplantation (BMT) is currently being evaluated in the treatment of MS in patients with aggressive disease activity. Autologous BMT could potentially reset the immune response to myelin antigens leading to immune tolerance and decreased disease activity. Allogeneic transplantation could reconstitute the immune system potentially arresting the progression of autoimmune disease. The purpose of this paper is to report a patient with MS who underwent allogeneic BMT for chronic myelogenous leukemia (CML) and showed continued evidence of active demyelinating disease by clinical and radiologic criteria over a period of two years. While this is only a single case report with inherent limitations, it suggests that the immune mediated destruction of CNS myelin in MS may not be prevented or aborted by immune system reconstitution, and is consistent with the idea that immune mediated tissue destruction in MS could be targeted against an abnormal antigen. Multiple Sclerosis 2007; 13: 1071—1075. http://msj.sagepub.com

Imaging of the immune system in multiple sclerosis patients using somatostatin

1998 ◽  
Vol 90 (1) ◽  
pp. 74
Author(s):  
S. Kam-Hansen ◽  
F. Mannting ◽  
C.R.G. Guttmann ◽  
H.L. Weiner
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Multiple Sclerosis Patients

Intracellular cytokine profile in T-cell subsets of multiple sclerosis patients: different features in primary progressive disease

2001 ◽  
Vol 7 (3) ◽  
pp. 145-150 ◽  
Author(s):  
J Killestein ◽  
B F Den Drijver ◽  
W L Van der Graaff ◽  
B MJ Uitdehaag ◽  
C H Polman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Peripheral Blood ◽  
T Cell Subsets ◽  
Primary Progressive ◽  
Immunoregulatory Cytokines ◽  
Immune Mediated ◽  
Distinct Disease ◽  
Circulating T Cells ◽  
Multiple Sclerosis Patients

Objective: To evaluate the expression of cytokines in both CD4+ and CD8+ T cells derived from peripheral blood of untreated multiple sclerosis (MS) patients with either relapsing-remitting (RR), secondary progressive (SP) or primary progressive (PP) MS and healthy controls (HC). Background: MS is an immune-mediated disease and cytokines have been hypothesized to contribute significantly to disease progression. Compared to the relapse-onset (RR, SP) form of the disease, PPMS patients have different clinical, immunological and pathological features. Surprisingly, the ability of their circulating T cells to produce immunoregulatory cytokines has not been extensively studied so far. Methods: Seventy-two MS patients (24 RR, 26 SP, 22 PP) and 34 HC were studied. Stimulated peripheral blood derived CD4+ and CD8+ T cells were analyzed for IFN-g, IL-2, TNF-a, IL-4, IL-10 and IL-13 production. Results: MS patients express significantly more CD4+ and CD8+ T cells producing IFN-g compared to HC. Compared to the other forms of the disease, PPMS patients display a significant decrease in CD4+ T cells producing IL-2, IL-13 and TNF-a and a significant increase in CD8+ T cells producing IL-4 and IL-10. Conclusions: The data presented here demonstrate that patients with PPMS express less pro- and more anti-inflammatory cytokine producing T cells compared to the relapse-onset form of the disease, confirming the view on PPMS as a distinct disease entity.

scholarly journals Immune-Mediated Colitis

2019 ◽  
Vol 17 (4) ◽  
pp. 506-523
Author(s):  
Tara Menon ◽  
Anita Afzali
Keyword(s):  
Inflammatory Bowel Disease ◽  
Monoclonal Antibodies ◽  
Immune System ◽  
Immune Checkpoint Inhibitors ◽  
Tumor Response ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Immune Mediated ◽  
Wide Range ◽  
Inflammatory Bowel

Abstract Purpose of review This review addresses our current knowledge of immune-mediated colitis (IMC) and offers a practical guide to its management. Recent findings Due to the similarity in clinical, endoscopic, and histologic findings between IMC and inflammatory bowel disease (IBD), gastroenterologists have tailored their approach to IMC management to that of IBD. Summary Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that augment the T-cell anti-tumor response of the immune system and have demonstrated their importance in the treatment of a wide range of malignancies. With the growing benefits of ICIs, there are immune-related adverse events (irAEs) that mirror many known autoimmune diseases. Diarrhea and IMC are the most common and severe irAEs noted. No standardized guidelines exist in the management of these irAEs.

Effect of ofatumumab versus placebo in relapsing multiple sclerosis patients from Japan and Russia: Phase 2 APOLITOS study

2021 ◽  
pp. 135245852110559
Author(s):  
Jun-ichi Kira ◽  
Jin Nakahara ◽  
Denis V Sazonov ◽  
Takayoshi Kurosawa ◽  
Isao Tsumiyama ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Opportunistic Infections ◽  
Open Label ◽  
Double Blind ◽  
Rate Versus ◽  
Open Label Extension ◽  
Clinical Benefits ◽  
Anti Cd20 ◽  
Multiple Sclerosis Patients ◽  
Relapsing Multiple Sclerosis

Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, has been developed as a treatment for relapsing multiple sclerosis (RMS) which can be self-administered at home. Objective: To investigate the efficacy and safety of ofatumumab in RMS patients from Japan and Russia. Methods: APOLITOS included a 24-week, double-blind, placebo-controlled core-part followed by an open-label extension-part. Patients were randomized (2:1) to subcutaneous ofatumumab 20 mg or placebo. Primary outcome was the number of gadolinium-enhancing (Gd+) T1 lesions per scan over 24 weeks. Results: Sixty-four patients were randomized (ofatumumab, n = 43; placebo, n = 21). Primary endpoint was met; ofatumumab reduced Gd + T1 lesions versus placebo by 93.6% ( p < 0.001) and the results were consistent across regions (Japan/Russia). Ofatumumab reduced annualized T2 lesion and relapse rate versus placebo by week 24. Both groups showed benefit from ofatumumab in the extension-part. Incidence of adverse events was lower with ofatumumab versus placebo (69.8% vs 81.0%); injection-related reactions were most common. No deaths, opportunistic infections, or malignancies were reported. Conclusion: Ofatumumab demonstrated superior efficacy versus placebo, with sustained effect through 48 weeks in RMS patients from Japan/Russia. Switching to ofatumumab after 24 weeks led to rapid radiological and clinical benefits. Safety findings were consistent with pivotal trials.

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