Multiple sclerosis: Serum-derived exosomes express myelin proteins

2017 ◽  
Vol 24 (4) ◽  
pp. 449-458 ◽  
Author(s):  
Grazyna Galazka ◽  
Marcin P Mycko ◽  
Igor Selmaj ◽  
Cedric S Raine ◽  
Krzysztof W Selmaj
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Cell Communication ◽  
Proteolipid Protein ◽  
Cell Receptor ◽  
Myelin Proteins ◽  
Strongly Correlated ◽  
Peripheral Blood Mononuclear ◽  
The Central Nervous System ◽  
Serum Exosomes

Background: Exosomes are small extracellular vesicles that provide cell-to-cell communication and are involved in immunoregulation. Objective: To investigate serum exosomes for the presence of myelin proteins outside the central nervous system (CNS) and their role in multiple sclerosis (MS). Methods: Serum, cerebrospinal fluid (CSF), and peripheral blood mononuclear cell (PBMC) samples were collected from 45 patients with relapsing–remitting MS (RRMS), 30 patients with secondary progressive MS (SPMS), and 45 healthy controls. Exosomes were isolated using a polymer formulation method, and their size, concentration, and CNS myelin protein contents were measured by a nanoparticle tracking analysis, enzyme-linked immunosorbent assays, and Western blot. Results: We found that exosomes expressed three major myelin proteins, myelin basic protein, proteolipid protein, and myelin oligodendrocyte glycoprotein (MOG). Exosomal content of MOG strongly correlated with disease activity and was highest in RRMS patients in relapse and in SPMS patients. Serum-derived exosomes induced proliferation of MOG-T cell receptor transgenic T cells confirming that serum exosomes maintained MOG immunogenicity. Conclusion: Exosomes isolated outside CNS tissue expressed myelin proteins, and the presence of MOG correlated strongly with disease activity. We conclude that exosomes might enhance and/or perpetuate anti-myelin immune reactions in MS and may provide novel markers of disease activity.

scholarly journals Recent Advances in Antigen-Specific Immunotherapies for the Treatment of Multiple Sclerosis

2020 ◽  
Vol 10 (6) ◽  
pp. 333 ◽  
Author(s):  
Olga Kammona ◽  
Costas Kiparissides
Keyword(s):  
Multiple Sclerosis ◽  
Cell Receptor ◽  
Myelin Proteins ◽  
Dna Encoding ◽  
Disease Modifying Therapies ◽  
Tolerogenic Dendritic Cells ◽  
The Central Nervous System ◽  
Myelin Antigens ◽  
Shed Light

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system and is considered to be the leading non-traumatic cause of neurological disability in young adults. Current treatments for MS comprise long-term immunosuppressant drugs and disease-modifying therapies (DMTs) designed to alter its progress with the enhanced risk of severe side effects. The Holy Grail for the treatment of MS is to specifically suppress the disease while at the same time allow the immune system to be functionally active against infectious diseases and malignancy. This could be achieved via the development of immunotherapies designed to specifically suppress immune responses to self-antigens (e.g., myelin antigens). The present study attempts to highlight the various antigen-specific immunotherapies developed so far for the treatment of multiple sclerosis (e.g., vaccination with myelin-derived peptides/proteins, plasmid DNA encoding myelin epitopes, tolerogenic dendritic cells pulsed with encephalitogenic epitopes of myelin proteins, attenuated autologous T cells specific for myelin antigens, T cell receptor peptides, carriers loaded/conjugated with myelin immunodominant peptides, etc.), focusing on the outcome of their recent preclinical and clinical evaluation, and to shed light on the mechanisms involved in the immunopathogenesis and treatment of multiple sclerosis.

scholarly journals Made to Measure: Patient-Tailored Treatment of Multiple Sclerosis Using Cell-Based Therapies

2021 ◽  
Vol 22 (14) ◽  
pp. 7536
Author(s):  
Inez Wens ◽  
Ibo Janssens ◽  
Judith Derdelinckx ◽  
Megha Meena ◽  
Barbara Willekens ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Autoimmune Diseases ◽  
Stromal Cells ◽  
Mononuclear Cells ◽  
Treatment Options ◽  
Cell Types ◽  
Peripheral Blood Mononuclear ◽  
Tailored Treatment ◽  
Key Issues ◽  
The Central Nervous System

Currently, there is still no cure for multiple sclerosis (MS), which is an autoimmune and neurodegenerative disease of the central nervous system. Treatment options predominantly consist of drugs that affect adaptive immunity and lead to a reduction of the inflammatory disease activity. A broad range of possible cell-based therapeutic options are being explored in the treatment of autoimmune diseases, including MS. This review aims to provide an overview of recent and future advances in the development of cell-based treatment options for the induction of tolerance in MS. Here, we will focus on haematopoietic stem cells, mesenchymal stromal cells, regulatory T cells and dendritic cells. We will also focus on less familiar cell types that are used in cell therapy, including B cells, natural killer cells and peripheral blood mononuclear cells. We will address key issues regarding the depicted therapies and highlight the major challenges that lie ahead to successfully reverse autoimmune diseases, such as MS, while minimising the side effects. Although cell-based therapies are well known and used in the treatment of several cancers, cell-based treatment options hold promise for the future treatment of autoimmune diseases in general, and MS in particular.

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 Emergence of three myelin proteins in oligodendrocytes cultured without neurons.

1986 ◽  
Vol 102 (2) ◽  
pp. 384-392 ◽  
Author(s):  
M Dubois-Dalcq ◽  
T Behar ◽  
L Hudson ◽  
R A Lazzarini
Keyword(s):  
Optic Nerve ◽  
Proteolipid Protein ◽  
Defined Medium ◽  
Myelin Proteins ◽  
Specific Marker ◽  
The Central Nervous System ◽  
Double Label ◽  
Myelin Associated Glycoprotein

Oligodendrocytes, the myelin-forming cells of the central nervous system, were cultured from newborn rat brain and optic nerve to allow us to analyze whether two transmembranous myelin proteins, myelin-associated glycoprotein (MAG) and proteolipid protein (PLP), were expressed together with myelin basic protein (MBP) in defined medium with low serum and in the absence of neurons. Using double label immunofluorescence, we investigated when and where these three myelin proteins appeared in cells expressing galactocerebroside (GC), a specific marker for the oligodendrocyte membrane. We found that a proportion of oligodendrocytes derived from brain and optic nerve invariably express MBP, MAG, and PLP about a week after the emergence of GC, which occurs around birth. In brain-derived oligodendrocytes, MBP and MAG first emerge between the fifth and the seventh day after birth, followed by PLP 1 to 2 d later. All three proteins were confined to the cell body at that time, although an extensive network of GC positive processes had already developed. Each protein shows a specific cytoplasmic localization: diffuse for MBP, mostly perinuclear for MAG, and particulate for PLP. Interestingly, MAG, which may be involved in glial-axon interactions, is the first myelin protein detected in the processes at approximately 10 d after birth. MBP and PLP are only seen in these locations after 15 d. All GC-positive cells express the three myelin proteins by day 19. Simultaneously, numerous membrane and myelin whorls accumulate along the oligodendrocyte surface. The sequential emergence, cytoplasmic location, and peak of expression of these three myelin proteins in vitro follow a pattern similar to that described in vivo and, therefore, are independent of continuous neuronal influences. Such cultures provide a convenient system to study factors regulating expression of myelin proteins.

Longitudinal single-cell cytokine responses reveal recurrent autoimmune myelin reactivity in relapsing-remitting multiple sclerosis patients

2005 ◽  
Vol 11 (3) ◽  
pp. 251-260 ◽  
Author(s):  
I R Moldovan ◽  
R A Rudick ◽  
A C Cotleur ◽  
S E Born ◽  
J-C Lee ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Amino Acid ◽  
Ex Vivo ◽  
Proteolipid Protein ◽  
Myelin Proteins ◽  
Immune Reactivity ◽  
Cytokine Responses ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients ◽  
Over Time

The relationship between multiple sclerosis (MS) disease activity and myelin protein-induced cytokine responses over time is not elucidated. We addressed this relationship by examining longitudinal cytokine responses to myelin proteins every three months for one year, in the context of gadolinium (gad)-enhancing brain lesions and of clinical relapses. The ELISPOT assay was used to determine the ex vivo cytokine production in response to nine amino acid long peptides spanning the entire proteolipid protein (PLP) and myelin basic protein (MBP) molecules in relapsing—remitting (RR) MS patients and matched healthy controls. We identified three longitudinal levels of myelin-induced cytokine secretion by adding up the positive responses for all PLP or MBP peptides obtained for five timepoints, at three- month intervals: low reactivity (<200 cumulative cytokine-secreting cells), isolated peptide reactivity (201-450 cumulative cytokine- secreting cells) and recurrent protein-wide bursts of cytokine reactivity (> 451 cumulative cytokine-secreting cells). The majority of MS patients showed recurrent bursts to PLP and MBP. In contrast, controls showed a more even distribution between all levels of cytokine reactivity. The majority of patients with gad-enhancing lesions showed PLP/IFNg and MBP/IFNg recurrent burst responses. This is the first longitudinal study on MS patients in which nine amino acid long myelin peptides are used to reveal the broad range of PLP- and MBP- peptide cytokine reactivity across the whole molecule of these two major myelin proteins. This study also reveals the extremely dynamic nature of the immune reactivity to numerous regions of myelin, which can fluctuate dramatically over time. Such fluctuation could hamper the efficacy of antigen-based therapies for MS.

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 Effects of multiple sclerosis in pregnant and post-birth: particularities of the disease activity

2021 ◽  
Author(s):  
Bianca Barbosa Araldi ◽  
Victor Hugo Gomes ◽  
Bruno Ludvig Vieira ◽  
Klesia Adayani Rodrigues ◽  
Andressa Gabrieli da Silva ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Neurological Diseases ◽  
Neuroprotective Effect ◽  
Cumulative Effect ◽  
Demyelinating Diseases ◽  
Hormonal Changes ◽  
Neuroprotective Effects ◽  
Maternal Immune System ◽  
The Central Nervous System

Introduction: Demyelinating diseases are a heterogeneous group of neurological diseases related to autoimmunity whose representative is Multiple Sclerosis (MS). It is characterized by an immune-mediated demyelination of the central nervous system, with a typical outbreak and remission clinic. During pregnancy, a reduction in disease activity was noted due to immunomodulatory effects, and an increase in outbreaks in the puerperium. Thus, our goal is to demonstrate the relationship between pregnancy and MS. Methods: This is a systematic bibliographic review based on searching the SCIELO, PUBMED and UPTODATE databases using the words “Multiple Sclerosis”, “Pregnancy”, “Demyelinating diseases” and “Neurological Disorders”. Discussion: Pregnancy is responsible for numerous changes in the maternal body resulting from hormonal changes with an immunological and neuroprotective effect. Until the beginning of the 20th century, it was considered a risk factor or precipitator of outbreaks in these patients. In 1950, Tillmann et al. questioned him and concluded that pregnancy reduces the risk of outbreaks of the disease and that relapses were more associated with postpartum. The question is still raised by several authors, due to their interest in the search for intricate protective factors in the genesis and cure of the disease. It is believed that immunological changes in pregnancy tend to suppress the maternal immune system preventing fetal rejection, and together with gestational hormones, they are able to make neuronal tissue more resistant to inflammatory aggression and greater capacity for cell repair. In the puerperium, there was an increase in outbreaks of the disease, probably associated with a reduction in hormone levels, the effects of which are lost after the elimination of the fetus. Breastfeeding is not associated with the prevention or risk of new MS outbreaks. The frequency of outbreaks before conception is the only independent predictor of new post-term episodes. There is no consensus regarding the therapeutic approach in these pregnant women. Conclusion: Evidence supports the association between pregnancy, reduced activity of MS and increased activity in the 3 months postpartum, due to the probable loss of neuroprotective effects associated with hormones. Recommendations regarding the use of immunomodulator are suspended before conception (“washout”) until term. New evidence did not associate the use of interferon-β with abortion, cesarean section or low birth weight. There was a benefit of long-term parity with a cumulative effect on the patient’s immunohumor modulation.

Disease activity and the immune set in multiple sclerosis: blood markers for immunotherapy

1998 ◽  
Vol 4 (3) ◽  
pp. 232-238 ◽  
Author(s):  
A J Coles ◽  
M G Wing ◽  
D AS Compston
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Immune Responses ◽  
Mononuclear Cells ◽  
Myelin Proteins ◽  
Peripheral Blood Mononuclear ◽  
Passive Measurement ◽  
Immunological Surveillance ◽  
Experimental Treatments

There is no established immunological marker of multiple sclerosis activity, which reflects the poor understanding of the immunopathogenesis of multiple sclerosis. Passive measurement of the levels of soluble inflammatory markers, whose half lives are usually measured in minutes and hours, can only indicate the extent of instantaneous inflammation, which is known to fluctuate in multiple sclerosis. We favour measurement of immune responses in vitro. As healthy individuals have T cell reactivities to myelin proteins that are postulated to be pathogenic in multiple sclerosis,1,2we prefer non-antigen specific mitogen and recall antigen assays as immunological markers. We illustrate their use in the treatment of 27 patients with multiple sclerosis using a pulse of humanised anti-lymphocyte (CD52) antibody that caused prolonged T cell depletion. The mitogen-induced proliferation, and secretion of IFN-g, from peripheral blood mononuclear cells in vitro was significantly reduced after treatment, suggesting that immune responses had been modulated. Such observations will only gain credence as an outcome measure if they are shown to correlate with clinical or radiological measures of multiple sclerosis activity. Perhaps more importantly, aspects of the pathogenesis of multiple sclerosis may be revealed by close immunological surveillance of patients undergoing experimental treatments.

scholarly journals Inner nuclear layer and olfactory threshold are interlinked and reflect inflammatory activity in multiple sclerosis

2020 ◽  
Vol 6 (3) ◽  
pp. 205521732094573
Author(s):  
Gabriel Bsteh ◽  
Harald Hegen ◽  
Patrick Altmann ◽  
Klaus Berek ◽  
Michael Auer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Inner Nuclear Layer ◽  
Inflammatory Activity ◽  
Strongly Correlated ◽  
Olfactory Threshold ◽  
Short Term ◽  
Cross Sectional ◽  
Time Pattern ◽  
The Central Nervous System ◽  
Disease Modifying Treatment

Background Retinal inner nuclear layer (INL) and olfactory threshold (OT) are associated with inflammatory activity in multiple sclerosis (MS). Objective The study aims to investigate (a) whether there is an association of INL and OT in MS and (b) if changes in INL and OT follow a time pattern in relation to MS relapse. Methods We assessed INL by optical coherence tomography and OT by Sniffin’ Sticks in three different cohorts: a cross-sectional MS cohort ( n = 260), a longitudinal, 3-year cohort of MS ( n = 141) and healthy controls ( n = 30), and a longitudinal, 24-weeks cohort with acute MS relapse ( n = 28) and stable MS controls ( n = 27). Results Cross-sectionally, INL and OT were strongly correlated with number but not localization of relapse in the previous 12 months and INL correlated with OT. Longitudinally, INL was thicker and OT score was lower short term in times of relapse activity, but not long term and independent of relapse localization. In acute MS relapse, INL and OT were altered compared with stable MS, again, independent of relapse localization resolving over 12–24 weeks with faster approximation to stable MS after escalation of disease-modifying treatment. Conclusions INL and OT are interlinked markers of short-term inflammatory activity, following a nearly congruent time pattern and independent of relapse localization, possibly reflecting a proinflammatory state within the central nervous system.

Sign in / Sign up

Export Citation Format

Share Document