scholarly journals IL-2 and Mycobacterial Lipoarabinomannan as Targets of Immune Responses in Multiple Sclerosis Patients

2020 ◽  
Vol 8 (4) ◽  
pp. 500 ◽  
Author(s):  
Marco Bo ◽  
Magdalena Niegowska ◽  
Jessica Frau ◽  
GianPietro Sechi ◽  
Giannina Arru ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mycobacterium Avium Subspecies Paratuberculosis ◽  
Interleukin 2 ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Slight Reduction ◽  
Multiple Sclerosis Patients ◽  
The Impact ◽  
Ms Pathogenesis ◽  
Future Practice

Interleukin 2 (IL-2) is considered a key player in exacerbating multiple sclerosis (MS). Therapies targeting its receptor have been developed; however, a resolution of the disease and side effects are still an issue of concern. The involvement of other factors, such as Mycobacterium avium subspecies paratuberculosis (MAP) and envelope protein derived from human endogenous retrovirus type W (HERV-Wenv), in MS pathogenesis has been recently suggested. Here, we investigated the levels of antibodies (Abs) directed against IL-2 and HERV-Wenv in 108 MS patients, 34 patients affected by neuromyelitis optica spectrum disorder (NMOSD), and 137 healthy controls (HCs). Our results show increased levels of Abs specific to IL-2 and HERV-Wenv-su antigens in MS vs. HCs (p < 0.0001 for IL-2, p = 0.0004 for HERV-Wenv) and significantly decreased levels in NMOSD vs. MS. The assessment of different 12-month-long therapies on Abs against IL-2, HERV-Wenv, and MAP lipoarabinomannan (LAM) demonstrated the strongest effect on anti-LAM Abs (p = 0.018), a slight reduction of anti-IL-2 Abs, and small variations for anti-HERV-Wenv Abs. These results highlight the conclusion that the impact of therapy is more correlated with selected epitopes than with the therapeutic agent. Screening for anti-IL-2 and anti-HERV-Wenv Abs has a potential as additional future practice to distinguish between symptomatically similar MS and NMOSD.

scholarly journals The DNA Copy Number of Human Endogenous Retrovirus-W (MSRV-Type) Is Increased in Multiple Sclerosis Patients and Is Influenced by Gender and Disease Severity

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e53623 ◽  
Author(s):  
Marta Garcia-Montojo ◽  
María Dominguez-Mozo ◽  
Ana Arias-Leal ◽  
Ángel Garcia-Martinez ◽  
Virginia De las Heras ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Severity ◽  
Copy Number ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Dna Copy Number ◽  
Multiple Sclerosis Patients

A ntibodies against a human endogenous retrovirus and the preponderance of env splice variants in multiple sclerosis patients

2003 ◽  
Vol 9 (1) ◽  
pp. 6-15 ◽  
Author(s):  
T Christensen ◽  
P D Sørensen ◽  
H J Hansen ◽  
A Møller-Larsen
Keyword(s):  
Multiple Sclerosis ◽  
Dna Sequences ◽  
Splice Variant ◽  
Splice Variants ◽  
Endogenous Retrovirus ◽  
Autoimmune Response ◽  
Human Endogenous Retrovirus ◽  
Pathogenic Potential ◽  
Polymerase Chain ◽  
Multiple Sclerosis Patients

The human endogenous retrovirus HERV-H is associated with multiple sclerosis (MS). Previously performed reverse transcriptase-polymerase chain reactio ns (RT-PC R) on virion-RNA demonstrated sequence variants of the HERV-H family located in the particulate fraction of MS patient plasma samples and not in controls. In this study a significantly elevated level of antibodies towards peptides derived from HERV-H/RGH-2 DNA sequences in serum and cerebrospinal fluid (C SF) from MS patients is demonstrated. Further, Wistar rats immunized with purified virions develop a specific serologic response, indicating that some virion proteins are encoded by HERV-H-related sequences. A lso shown is that in RNA from blood cells, a HERV-H protease-env splice variant can be found together with an env splice variant in about 40% of MS patients but only in 10% of controls. The results substantiate the association between activated HERV-H and MS, but a causal relationship is yet to be demonstrated. HERV-H could represent a causal factor either by eliciting an autoimmune response or through the pathogenic potential of the retrovirus itself.

scholarly journals THE COMPARATIVE STUDY OF HUMAN ENDOGENOUS RETROVIRUS HERV-E λ 4-1 EXPRESSION IN BLOOD IMMUNE CELLS OF MULTIPLE SCLEROSIS PATIENTS

2019 ◽  
Vol 19 (1S) ◽  
pp. 78-80
Author(s):  
I A Goldina ◽  
E V Markova
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Mrna Level ◽  
Endogenous Retrovirus ◽  
Pokeweed Mitogen ◽  
Human Endogenous Retrovirus ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Multiple Sclerosis Patients

In order to investigate the function of human endogenous retrovirus HERV-E λ 4-1 in multiple sclerosis pathogenesis, the comparative research of frequency of this retrovirus expression and mRNA level on different types of blood immune cells of progredient course multiple sclerosis patients have been conducted with using of the reverse - transcriptase polymerase chain reaction method. Peripheral blood mononuclear cells were isolated on Ficoll density gradient centrifugations. Monocytes were separated by the adhesion to plastic Petri dishes. For the estimation of the mitogen-induced HERV-E λ 4-1 expression, blood mononuclear cells were incubated with adding of phytogemagglutinin or pokeweed mitogen during 72 hours in CO2 incubator at 37 °C and 5% CO2. Results of HERV-E λ 4-1 env gene expression estimation demonstrate that both monocytes and lymphocytes express HERV-E λ 4-1. The level of the HERV-E λ 4-1 env mRNA was higher in lymphocytes than in monocytes. The main source of HERV-E λ 4-1 in progredient course MS patients between blood immune cells are lymphocytes, especially B lymphocytes.

scholarly journals Human Endogenous Retrovirus Type W Envelope from Multiple Sclerosis Demyelinating Lesions Shows Unique Solubility and Antigenic Characteristics

2021 ◽  
Author(s):  
Benjamin Charvet ◽  
Justine Pierquin ◽  
Joanna Brunel ◽  
Rianne Gorter ◽  
Christophe Quétard ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Envelope Protein ◽  
Endogenous Retrovirus ◽  
Brain Lesions ◽  
Human Endogenous Retrovirus ◽  
Soluble Antigen ◽  
Physico Chemical ◽  
Demyelinating Lesions ◽  
Ms Pathogenesis

AbstractIn multiple sclerosis (MS), human endogenous retrovirus W family (HERV-W) envelope protein, pHERV-W ENV, limits remyelination and induces microglia-mediated neurodegeneration. To better understand its role, we examined the soluble pHERV-W antigen from MS brain lesions detected by specific antibodies. Physico-chemical and antigenic characteristics confirmed differences between pHERV-W ENV and syncytin-1. pHERV-W ENV monomers and trimers remained associated with membranes, while hexamers self-assembled from monomers into a soluble macrostructure involving sulfatides in MS brain. Extracellular hexamers are stabilized by internal hydrophobic bonds and external hydrophilic moieties. HERV-W studies in MS also suggest that this diffusible antigen may correspond to a previously described high-molecular-weight neurotoxic factor secreted by MS B-cells and thus represents a major agonist in MS pathogenesis. Adapted methods are now needed to identify encoding HERV provirus(es) in affected cells DNA. The properties and origin of MS brain pHERV-W ENV soluble antigen will allow a better understanding of the role of HERVs in MS pathogenesis. The present results anyhow pave the way to an accurate detection of the different forms of pHERV-W ENV antigen with appropriate conditions that remained unseen until now.

scholarly journals INVESTIGATION OF BLOOD MONONUCLEAR CELLS CYTOKINE-PRODUCTION FUNCTION FROM PATIENTS WITH MULTIPLE SCLEROSIS TREATED WITH THE ENDOGENOUS RETROVIRUS HERV-E λ 4-1 CONSERVATIVE REGION SYNTHETIC OLIGOPEPTIDE

2021 ◽  
Vol 23 (4) ◽  
pp. 749-754
Author(s):  
I. A. Goldina ◽  
E. V. Markova
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Culture Supernatant ◽  
Transmembrane Protein ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Healthy Individuals ◽  
Spontaneous Production ◽  
Blood Mononuclear Cells ◽  
Multiple Sclerosis Patients

Considering to the data of class I human endogenous retrovirus HERV-Е λ 4-1 subgroup association with multiple sclerosis, an autoimmune disease accompanied by neuroinflammation, changes in the neurotransmitters level, progressive neurological dysfunction, as well as the ability of this retrovirus to replicate and to produce proteins with potential immunomodulatory properties, the aim of this work was a comparative study of the blood immune cells cytokine synthesizing function in conventionally healthy individuals and multiple sclerosis patients under the synthetic 17 – amino acid oligopeptide homologous to the hydrophobic transmembrane protein р15Е HERV-Е λ 4-1 conserved region influence. The 40 patients, 17 male persons aged 38.0 (31.0-47.0) years old and 23 female persons aged 39.0 (31.0-50.0) years old with an established diagnosis of multiple sclerosis (G 35, ICD-10), corresponding to the McDonald 2005, modified in 2010 criteria with a continuously progressive disease course and the disease duration of 17.0 (14.0-18.0) years, and 30 conditionally healthy individuals, 12 male persons aged 32.0 (23.0-43.0) years old and 18 female persons aged 36.0 (29.0-46.0) years old were the objects of the study. An open-label, observational, single-center, cohort, controlled, randomized trial was conducted. It was found that the donor’s blood mononuclear cells IL-1β, IL-6, TNFα, IFNγ and IL-2 spontaneous production in culture was stimulated, but that of IL-4 and IL-10 did not change under the retroviral oligopeptide influence. At the same time, the spontaneous and mitogenstimulated production of all studied cytokines did not change under the control oligopeptide influence. The PHA-stimulated donor’s blood mononuclear cells cultivation in presence of the retroviral oligopeptide, as compared to the control one, was accompanied by an increase in the IL-1β, IL-6 and TNFα release into the culture supernatant. The multiple sclerosis patients were characterized by IL-1β, IL-6 and IFNγ higher content in the mitogen-unstimulated blood mononuclear cells culture supernatant, compared with conditionally healthy individuals, as well as by a higher production of IL-6 and IFNγ in response to PHA stimulation. The retroviral oligopeptide, in contrast to the control one, stimulated the IL-1β, IL-6, TNFα and IFNγ spontaneous production without altering that of IL-4 and IL-10 in multiple sclerosis patients. The obtained results indicate that the synthetic oligopeptide homologous to the conserved region of the hydrophobic transmembrane protein p15E HERV-Е λ 4-1 has the pro-inflammatory properties, which is probably the one of human endogenous retrovirus HERV-Е λ 4-1 pathological abilities realization mechanism in multiple sclerosis. 

scholarly journals Viruses in multiple sclerosis pathogenesis

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Rachael Tarlinton ◽  
Elena Morandi ◽  
Belinda Wang ◽  
Bruno Gran ◽  
Timur Khaiboullin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Risk Factor ◽  
Viral Infections ◽  
Inflammatory Responses ◽  
Molecular Mimicry ◽  
Endogenous Retrovirus ◽  
Neurological Dysfunction ◽  
Human Endogenous Retrovirus ◽  
Vitamin D Levels ◽  
Ms Pathogenesis

Multiple sclerosis (MS) is an extremely debilitating auto-immune disease of people characterised by demyelination of the central nervous system and progressive neurological dysfunction. The etiology of the disease is complex (including factors such as genetics, sex hormones and vitamin D levels). The involvement of viral infections as a risk factor in triggering disease has long been suspected and two classes of viruses in particular, the herpesvirus Epstein-Barr virus (EBV) and the Human endogenous retrovirus “W” family (HERV-W) have been the focus of much recent research. Despite near ubiquitious infection (EBV), or integration into the genome as a repetitive element no longer able to function as a virus (HERV-W) a picture is gradually emerging of how these are involved in MS pathogenesis. In the case of EBV, having had infectious mononucleosis (clinical disease in patients infected post-puberty) increases the risk of developing MS. For HERV-W our recent work has confirmed that RNA is over-expressed in MS patients compared with healthy controls (though basal levels vary with ethnic background) and that EBV infection of B cells triggers expression of HERV-W RNA and proteins. There is a growing body of evidence that expression of HERV-W can trigger innate immune system inflammatory responses. There is also increasing evidence for molecular mimicry between epitopes of the HERV-W env protein, the EBV EBNA1 protein and peptides from brain proteins implicated in MS pathogenesis. Crucially these peptides are also able to bind the HLA-DR2b locus that is the strongest genetic risk factor for MS development.

scholarly journals JC Virus Seroprevalence and JCVAb Index in Polish Multiple Sclerosis Patients Treated with Immunomodulating or Immunosuppressive Therapies

2021 ◽  
Vol 10 (9) ◽  
pp. 1998
Author(s):  
Robert Bonek ◽  
Wojciech Guenter ◽  
Robert Jałowiński ◽  
Anna Karbicka ◽  
Anna Litwin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Jc Virus ◽  
Dimethyl Fumarate ◽  
Risk Category ◽  
Seroprevalence Rate ◽  
Immunomodulatory Drugs ◽  
Cross Sectional ◽  
Treatment Type ◽  
Multiple Sclerosis Patients ◽  
The Impact

The use of a highly-effective treatment for multiple sclerosis (MS) is associated with a severe risk of developing complications, such as progressive multifocal leukoencephalopathy (PML) caused by the John Cunningham virus (JCV). The aim of this study was to evaluate the correlation between anti-JCV Ab seroprevalence, anti-JCV AI, demographic and clinical factors as well as the type of therapy used in the Polish MS population. This is a multicentre, prospective and cross-sectional study involving 1405 MS patients. The seroprevalence of anti-JCV Ab and anti-JCV AI levels as well as AI categories were analysed with the use of a second-generation two-step ELISA test (STRATIFY JCV DxSelect). The overall prevalence of anti-JCV Ab was 65.8%. It was shown that seroprevalence increases with the patient’s age. The seroprevalence was significantly associated with the treatment type, and the highest values (76%) were obtained from immunosuppressant-treated patients. Overall, 63.3% of seropositive patients had an antibody index (AI) level of >1.5. In the seropositive patient group, the mean AI level amounted to 2.09. Similarly to the seroprevalence, AI levels correlated with the patient’s age; AI level for patients above 40 years old and from subsequent age quintiles plateaued, amounting to at least 1.55. Patients treated with immunosuppressants and immunomodulatory drugs obtained the highest (1.67) and lowest (1.35) AI levels, respectively. Of the immunosuppressants used, the highest mean AI levels were observed in mitoxantrone and cladribine groups, amounting to 1.75 and 1.69, respectively. In patients treated with immunomodulatory drugs, the lowest AI levels were observed in the dimethyl fumarate (DMF) group (1.11). The seroprevalence rate in the Polish MS population is one of the highest in Europe. The majority of seropositive patients had an anti-JCV Ab level qualifying them for a high-risk category. The highest mean AI levels are observed in patients receiving immunosuppressants, especially mitoxantrone and cladribine. Patients receiving immunomodulatory drugs have lower AI levels compared to treatment-naïve subjects, especially when treated with DMF. Further studies, especially longitudinal studies, are required to determine the impact of MS drugs on the seroprevalence of anti-JCV Ab and AI levels.

scholarly journals Regulation of CTLA-4 and PD-L1 Expression in Relapsing-Remitting Multiple Sclerosis Patients after Treatment with Fingolimod, IFNβ-1α, Glatiramer Acetate, and Dimethyl Fumarate Drugs

2021 ◽  
Vol 11 (8) ◽  
pp. 721
Author(s):  
Afshin Derakhshani ◽  
Zahra Asadzadeh ◽  
Hossein Safarpour ◽  
Patrizia Leone ◽  
Mahdi Abdoli Shadbad ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Demyelinating Disease ◽  
Immune Checkpoints ◽  
Peripheral Blood Mononuclear ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Impact

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) that is characterized by inflammation which typically results in significant impairment in most patients. Immune checkpoints act as co-stimulatory and co-inhibitory molecules and play a fundamental role in keeping the equilibrium of the immune system. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and Programmed death-ligand 1 (PD-L1), as inhibitory immune checkpoints, participate in terminating the development of numerous autoimmune diseases, including MS. We assessed the CTLA-4 and PD-L1 gene expression in the different cell types of peripheral blood mononuclear cells of MS patients using single-cell RNA-seq data. Additionally, this study outlines how CTLA-4 and PD-L1 expression was altered in the PBMC samples of relapsing-remitting multiple sclerosis (RRMS) patients compared to the healthy group. Finally, it investigates the impact of various MS-related treatments in the CTLA-4 and PD-L1 expression to restrain autoreactive T cells and stop the development of MS autoimmunity.

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