scholarly journals The STING-IFN-β-Dependent Axis Is Markedly Low in Patients with Relapsing-Remitting Multiple Sclerosis

2020 ◽  
Vol 21 (23) ◽  
pp. 9249
Author(s):  
Lars Masanneck ◽  
Susann Eichler ◽  
Anna Vogelsang ◽  
Melanie Korsen ◽  
Heinz Wiendl ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Type I ◽  
Autoimmune Encephalomyelitis ◽  
Beneficial Effects ◽  
Endogenous Production ◽  
Relapsing Remitting ◽  
Peripheral Lymphoid Tissue ◽  
The Central Nervous System ◽  
Peripheral Immune Cells ◽  
Relapsing Remitting Multiple Sclerosis

Cyclic GMP-AMP-synthase is a sensor of endogenous nucleic acids, which subsequently elicits a stimulator of interferon genes (STING)-dependent type I interferon (IFN) response defending us against viruses and other intracellular pathogens. This pathway can drive pathological inflammation, as documented for type I interferonopathies. In contrast, specific STING activation and subsequent IFN-β release have shown beneficial effects on experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Although less severe cases of relapse-remitting MS (RRMS) are treated with IFN-β, there is little information correlating aberrant type I IFN signaling and the pathologic conditions of MS. We hypothesized that there is a link between STING activation and the endogenous production of IFN-β during neuroinflammation. Gene expression analysis in EAE mice showed that Sting level decreased in the peripheral lymphoid tissue, while its level increased within the central nervous system over the course of the disease. Similar patterns could be verified in peripheral immune cells during the acute phases of RRMS in comparison to remitting phases and appropriately matched healthy controls. Our study is the first to provide evidence that the STING/IFN-β-axis is downregulated in RRMS patients, meriting further intensified research to understand its role in the pathophysiology of MS and potential translational applications.

Ingested IFN-α has biological effects in humans with relapsing-remitting multiple sclerosis

1997 ◽  
Vol 3 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Staley A Brod ◽  
Ronald H Kerman ◽  
Laura D Nelson ◽  
Gailen D Marshall ◽  
Evelyn M Henninger ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Biological Effects ◽  
Intercellular Adhesion Molecule ◽  
Type I ◽  
Recombinant Type ◽  
Relapsing Remitting ◽  
Ifn Γ ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Parenterally administered human recombinant type I interferons (hrIFN) in relapsing-remitting multiple sclerosis (RRMS) decrease relapses and spontaneous in vitro IFN-γ production, reduce clinical progression, and decrease magnetic resonance imaging (MRI)-defined disease activity and lesions. Parenterally administered type I IFN use is limited by clinical and chemical toxicities, and the induction of antibodies that abrogate their activity in vivo correlated with the loss of clinical benefit. Therefore, we determined whether ingested IFN-α was non-toxic and had biological effects in humans. ingested hrIFN-α showed no toxicity in normal volunteers or patients with RRMS at doses ranging from 300 to 100 000 units. In subjects with RRMS, a significant decrease in Con A-mediated proliferation and serum soluble intercellular adhesion molecule-I (sICAM-I), a surrogate measure for disease activity in MS, was found after ingesting 10 000 and 30 000 units IFN-α The RRMS subjects also showed decreased IL-2 secretion after ingesting 10 000 units IFN-α, and decreased IFN-γ, TGF-β and IL-10 production after ingesting 30 000 units IFN-α. The decreased secretion of IFN-γ and IL-2 by ingested IFN-α suggests that oral IFN-α may cause a functional inhibition of Th I-like T helper cells in RRMS, a potential site of intervention at the level of effector T cells in MS. Our studies support the oral use of human IFN-α as a biological response modifier in humans.

scholarly journals Innate Immune System and Multiple Sclerosis. Granulocyte Numbers Are Reduced in Patients Affected by Relapsing-Remitting Multiple Sclerosis during the Remission Phase

2020 ◽  
Vol 9 (5) ◽  
pp. 1468
Author(s):  
Zbyšek Pavelek ◽  
Francesco Angelucci ◽  
Ondřej Souček ◽  
Jan Krejsek ◽  
Lukáš Sobíšek ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Innate Immunity ◽  
Innate Immune ◽  
Healthy Controls ◽  
Statistical System ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Remission Phase ◽  
Relapsing Remitting Multiple Sclerosis

Background: Multiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system. The cause of MS is still unknown, and the role of innate immunity is still poorly understood. Objective: The goal of this study was to understand whether, compared to healthy controls, the elements of innate immunity are altered in the blood of MS patients in the remitting phase. Methods: A total of 77 naïve MS patients and 50 healthy controls were included in this cohort study. Peripheral blood samples were collected and analyzed. All the calculations were performed with the statistical system R (r-project.org). Results: The results showed that MS patients had significantly lower relative representations of granulocytes than healthy controls, while the relative representations of monocytes remained unchanged. CD64- and PD-L1-positive granulocytes exhibited a nonsignificant decreasing trend, while granulocytes with other membrane markers remained noticeably unchanged. Conclusion: The results of this study suggest that studies of the causes of MS and its treatment should also be focused on the elements of the innate immune response.

First use of alemtuzumab in Balo’s concentric sclerosis: a case report

2013 ◽  
Vol 19 (12) ◽  
pp. 1673-1675 ◽  
Author(s):  
JWL Brown ◽  
AJ Coles ◽  
JL Jones
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibody ◽  
Standard Protocol ◽  
Demyelinating Disorder ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Radiological Impact ◽  
Treatment Refractory ◽  
Baló’S Concentric Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Balo’s concentric sclerosis (BCS) is a rare demyelinating disorder of the central nervous system. The humanised monoclonal antibody alemtuzumab has shown efficacy in another demyelinating disorder, relapsing–remitting multiple sclerosis. We aimed to explore its efficacy in treatment-refractory BCS. A 52-year-old male with radiologically confirmed progressive BCS resistant to steroids, plasmapharesis and cyclophosphamide was administered a standard protocol of alemtuzumab. Treatment failed to slow his decline; he died 6 months after administration. Why alemtuzumab induced no clinical or radiological impact may be multifactorial. We review the evidence directing BCS therapy and propose the next steps for exploring this potentially fatal condition.

Relapsing-Remitting Multiple Sclerosis - Current Treatment Options and Perspectives for the Future

2010 ◽  
Vol 5 (1) ◽  
pp. 78
Author(s):  
Alex Rae-Grant ◽  
Daniel Ontaneda ◽  
◽  
Keyword(s):  
Multiple Sclerosis ◽  
Treatment Options ◽  
Current Treatment ◽  
Relapsing Remitting ◽  
Significant Disability ◽  
The Central Nervous System ◽  
Disease Modifying Agents ◽  
Phase Ii And Iii ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Made In

Multiple sclerosis (MS) is the most prevalent demyelinating condition of the central nervous system and produces significant disability over time. For many years it was considered to be an untreatable disease, but great advances have been made in the treatment of MS in the last 20 years. There are currently six US Food and Drug Administration (FDA)-approved disease-modifying agents for the relapsing form of the disease. We review in detail these medications and the pivotal trials leading to their approval. We will briefly review non-FDA-approved medications already used in MS. We will also discuss some of the medications currently being studied in phase II and III trials that are not yet approved for use in MS.

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.

Rapid benefits of a new formulation of subcutaneous interferon beta-1a in relapsing—remitting multiple sclerosis

2010 ◽  
Vol 16 (7) ◽  
pp. 888-892 ◽  
Author(s):  
Nicola De Stefano ◽  
François Curtin ◽  
Bettina Stubinski ◽  
Gregg Blevins ◽  
Jelena Drulovic ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Mri ◽  
Cumulative Number ◽  
Beneficial Effects ◽  
Relapsing Remitting ◽  
The Mean ◽  
Remitting Multiple Sclerosis ◽  
New Formulation ◽  
Post Hoc ◽  
Relapsing Remitting Multiple Sclerosis

This study evaluated the efficacy of a new formulation of subcutaneous (sc) interferon (IFN)-β1a in relapsing—remitting multiple sclerosis (RRMS). Patients ( n = 180) were randomized (2 : 1) to IFN-β1a or placebo for 16 weeks; all patients then received IFN-β1a for 24 weeks. Monthly brain MRI was performed. At week 16, the mean number of combined unique active (CUA) lesions was lower with IFN-β1a than with placebo ( p < 0.001; 69% fewer lesions). The mean cumulative number of CUA lesions was already lower with IFN-β1a by week 4 (post hoc analysis; p = 0.015). The new formulation of sc IFN-β1a has rapid beneficial effects on MRI outcomes in RRMS.

IFN-β treatment modulates the CD28/CTLA-4-mediated pathway for IL-2 production in patients with relapsing -remitting multiple sclerosis

2004 ◽  
Vol 10 (6) ◽  
pp. 630-635 ◽  
Author(s):  
C Espejo ◽  
L Brieva ◽  
G Ruggiero ◽  
J Río ◽  
X Montalban ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Chronic Inflammatory Disease ◽  
Autoimmune Response ◽  
T Cell Proliferation ◽  
Immunomodulatory Effects ◽  
Cd25 Expression ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Relapsing Remitting Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system probably mediated by Th1 lymphocytes. IFN-b is an established therapy for relapsing MS patients, although the mechanisms underlying its efficacy are yet to be well characterized. We determined IL-2 production, CD25 expression and T-cell proliferation from relapsing -remitting MS patients before and three months after starting therapy. A decrease in the percentage of CD80-induced IL-2-producing cells was observed after in vivo IFN-b treatment. These data support that one of the immunomodulatory effects of IFN-b treatment in MS may be a limitation of the autoimmune response modifying the CD80:CD28/CTLA-4 pathway.

Biological markers in body fluids for activity and progression in multiple sclerosis

1999 ◽  
Vol 5 (4) ◽  
pp. 287-290
Author(s):  
Per Soelberg Sùrensen
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Biological Markers ◽  
Body Fluids ◽  
Therapeutic Effects ◽  
Therapeutic Decisions ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
The Individual ◽  
Relapsing Remitting Multiple Sclerosis

Reliable biological markers in body fluids for disease activity and progression are important for our understanding of the pathophysiology and therapeutic decisions in various subtypes of multiple sclerosis. Sampling from body fluids such as cerebrospinal fluid, blood, and urine constitutes the problem that the local immuno-inflammatory process takes place in the central nervous system whereas the disease activity is only to some extent reflected in the systemic immune compartment. Promising results have been obtained in studies of adhesion molecules, pro-inflammatory cytokines, co-stimulatory molecules and neopterin as markers of disease activity in relapsing-remitting multiple sclerosis. However, these results apply to groups of patients but not necessarily to individual patients. Currently no single body fluid marker is sufficiently correlated to disease activity to be used in the individual patient in monitoring disease activity, progression, or therapeutic effects.

scholarly journals Assessment of the influence of various risk factors on the severity of psycho-emotional disorders in patients with multiple sclerosis

2021 ◽  
Vol 17 (5) ◽  
pp. 31-35
Author(s):  
T.A. Odintsova ◽  
O.O. Kopchak
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Emotional Disorders ◽  
Demyelinating Disease ◽  
External Factors ◽  
Depression And Anxiety ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Severity Levels ◽  
Relapsing Remitting Multiple Sclerosis

Multiple sclerosis is an insidious disabling, both physically and mentally, demyelinating disease of the central nervous system. People with multiple sclerosis, apart from the classic manifestations, can also experience depression and anxiety. The study was aimed to assess peculiarities of influence of socio-demographic, external factors, and characteristics of the disease on depression and anxiety among patients with relapsing-remitting multiple sclerosis. The following article highlights the main risk factors and their ways of influence on the aforementioned disorders, distinguished by the multifactorial analysis. Also, it estimates the frequency of different severity levels of either depression or anxiety depending on the pre-sence of each risk factor.

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