Article
Immunology
Jeremy T. Keane, Ali Afrasiabi, Stephen D. Schibeci, Nicole Fewings, Grant P. Parnell, Sanjay Swaminathan, David R. Booth
Summary: The study found gender-specific associations with EBV traits and MS risk SNP/gene pairs, with some genes showing gender differences in correlation of gene expression level with Estrogen Receptor 2. Estradiol treatment altered MS risk gene expression, LCL proliferation rate, EBV DNA copy number, and EBNA2 expression in a sex-dependent manner, indicating estrogen-mediated gender-specific differences in MS risk gene expression and EBV functions. This may contribute to gender differences in host response to EBV and MS susceptibility.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Yoshimi Enose-Akahata, Limin Wang, Fahad Almsned, Kory R. Johnson, Yair Mina, Joan Ohayon, Xin Wei Wang, Steven Jacobson
Summary: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), and the cause of MS remains unknown. This study investigated the antibody responses against various viruses in the cerebrospinal fluid (CSF) and serum of MS patients, and found significant differences compared to healthy volunteers, as well as a pattern of antibody responses against multiple viruses, including Epstein-Barr virus. These findings indicate that virus-specific antibody signatures might reflect the disease-associated inflammatory milieu in the CSF of patients with neuroinflammatory diseases.
Review
Microbiology
Cyril Debuysschere, Magloire Pandoua Nekoua, Didier Hober
Summary: Viral infections, particularly Epstein-Barr virus (EBV), have long been suspected to play a role in the development and progression of autoimmune diseases such as multiple sclerosis (MS), lupus, rheumatoid arthritis, Sjogren's syndrome, and type 1 diabetes. EBV has a complex lifecycle in infected B-cells, producing viral proteins and miRNAs. This review highlights the detection of EBV infection in MS patients, focusing on markers of latency and lytic phases. The presence of latency proteins, antibodies, and miRNAs in the central nervous system of MS patients suggests a link between EBV and MS.
Review
Immunology
Jessica Frau, Giancarlo Coghe, Lorena Lorefice, Giuseppe Fenu, Eleonora Cocco
Summary: Multiple Sclerosis (MS) is an inflammatory disease of the central nervous system, with Sardinia having one of the highest prevalence rates. Infections, genetic factors, and Human endogenous retroviruses (HERV) have been associated with the development of MS.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Hematology
Hannes Vietzen, Philippe L. Furlano, Jan J. Cornelissen, Georg A. Boehmig, Peter Jaksch, Elisabeth Puchhammer-Stoeckl
Summary: This study found that nonclassic human leukocyte antigen E (HLA-E)-restricted immune responses have a significant impact on the development of Epstein-Barr virus (EBV) diseases in the individual host. The highly expressed HLA-E*0103/0103 genotype is protective against infectious mononucleosis (IM) by inducing potent EBV BZLF1-specific HLA-E-restricted CD8(+) T-cell responses. Variations in the inhibitory NKG2A/LMP-1/HLA-E axis are associated with the risk of symptomatic EBV reactivations in both immunocompetent individuals and immunocompromised transplant recipients.
Review
Virology
Luwen Zhang
Summary: In this article, the authors propose that EBV can act as both an autoimmune initiator and promoter in autoimmune diseases. Different types of latency cells of EBV can enhance the development of autoimmune diseases and cause inflammatory cytokine production. The replenishment frequency of EBV latency cells may determine the specific effects of the promoter functions. A combination of a specific initiator and EBV-mediated promoter function may lead to the development of specific autoimmune diseases and link EBV infection to a variety of autoimmunity.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Mireya Fernandez-Fournier, Maripaz Lopez-Molina, Gabriel Torres Iglesias, Lucia Botella, Beatriz Chamorro, Fernando Laso-Garcia, Inmaculada Puertas, Antonio Tallon Barranco, Laura Otero-Ortega, Ana Frank-Garcia, Exuperio Diez-Tejedor
Summary: This study aimed to investigate the presence of antibodies against EBV antigens in EVs and their potential as diagnostic and disease activity blood biomarkers in RRMS. The results showed that patients with RRMS had higher levels of anti-VCA antibodies in EVs and plasma compared to healthy controls. Patients with active disease also had higher levels of anti-EBNA1 antibodies in EVs. Furthermore, the levels of EV anti-VCA correlated with disease duration and decreased brain volume structures in RRMS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Massimiliano Castellazzi, Caterina Ferri, Alice Piola, Samantha Permunian, Gaia Buscemi, Michele Laudisi, Eleonora Baldi, Maura Pugliatti
Summary: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease associated with the Epstein-Barr virus (EBV). In this study, we investigated the effects of dimethyl fumarate (DMF), a first-line treatment for MS, on the quantity and quality of EBV-specific IgG in MS patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Immunology
Tomas Olsson
Summary: MS is a multifactorial disease with genetic and environmental factors contributing to its etiology. HLA-DR15 and EBV are key factors increasing the risk of the disease, with the study showing higher viral load and immune response in HLA-DR15 carriers infected with EBV compared to non-carriers, potentially exacerbating MS.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Clinical Neurology
Klaus Rostgaard, Nete Munk Nielsen, Mads Melbye, Morten Frisch, Henrik Hjalgrim
Summary: Epstein-Barr virus infection is a prerequisite for the development of multiple sclerosis, particularly delayed infections. Siblings provide protection against infectious mononucleosis by occasionally preventing delayed primary Epstein-Barr virus infection. The age difference between siblings determines the level of protection, with closer age gaps providing higher protection.
Review
Immunology
Corey Smith, Rajiv Khanna
Summary: The link between Epstein-Barr virus (EBV) and multiple sclerosis has led to the development of immune-based therapies targeting EBV-infected B cells. Initial studies with autologous EBV-specific T-cell therapy have shown safety and improvements in neurological symptoms and objective measures. Allogeneic EBV-specific T-cell therapy, derived from healthy donors, has also demonstrated safety and promising clinical responses, offering potential advantages over autologous therapy.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2023)
Review
Immunology
Gianmarco Bellucci, Virginia Rinaldi, Maria Chiara Buscarinu, Roberta Renie, Rachele Bigi, Giulia Pellicciari, Emanuele Morena, Carmela Romano, Antonio Marrone, Rosella Mechelli, Marco Salvetti, Giovanni Ristori
Summary: There is a long-standing association between MS and viral infections, with the novel Coronavirus, SARS-CoV-2, having a significant impact on the immune system that echoes several aspects of MS pathobiology. Studying COVID-19 in people with MS has helped clinicians adjust therapeutic strategies, and efforts are being made for SARS-CoV-2 vaccination campaigns in this population.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
Yin Xu, Ayako Hiyoshi, Kelsi A. Smith, Fredrik Piehl, Tomas Olsson, Katja Fall, Scott Montgomery
Summary: The study suggests that having infectious mononucleosis in childhood and especially adolescence is a risk factor associated with a diagnosis of multiple sclerosis, independent of shared familial factors.
Review
Immunology
Gianmarco Bellucci, Angela Albanese, Caterina Rizzi, Virginia Rinaldi, Marco Salvetti, Giovanni Ristori
Summary: Interferon-beta (IFN-beta) for Multiple Sclerosis (MS) is celebrating its 30th anniversary. The COVID-19 pandemic has reignited interest in the biology of interferon in health and disease, expanding its potential applications beyond neuroinflammation. The antiviral properties of IFN-beta align with the viral etiology hypothesis of MS, particularly in relation to the Epstein-Barr Virus. Furthermore, IFNs play a crucial role in the acute phase of SARS-CoV-2 infection, and IFN-beta has shown protective effects against SARS-CoV-2 in individuals with MS.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Tobias Lanz, William H. Robinson, Peggy P. Ho, Lawrence Steinman
Summary: We propose studying the molecular mechanisms underlying the clonal antibody response in cerebrospinal fluid and exploring therapeutic approaches to block EBV-triggered multiple sclerosis. These include antiviral clinical trials, development of nucleic acid-based vaccines, cellular adoptive therapy, and vaccines to EBV. These topics are not exhaustive, but our medical science community has the tools to tackle EBV-triggered MS and potentially eradicate the disease, as we have done with poliomyelitis.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2023)
Editorial Material
Clinical Neurology
R. J. E. Armstrong, J. Downer, N. Evans, P. Anslow, G. C. Ebers
Article
Clinical Neurology
A. Dessa Sadovnick, Irene M. Yee, Maria Criscuoli, Gabriele C. DeLuca
Summary: The study evaluated the impact of temporal increase of female to male sex ratio on the familial risk for individuals with multiple sclerosis. Genetic sharing and environmental factors were found to both play important roles in determining familial risk. An increase in MS risk due to environmental factors was observed over time, particularly for sisters/brothers of female probands.
MULTIPLE SCLEROSIS JOURNAL
(2022)
Article
Clinical Neurology
Kristen M. Krysko, Annika Anderson, Jessica Singh, Kira McPolin, Alice Rutatangwa, William Rowles, A. Dessa Sadovnick, Maria K. Houtchens, Riley Bove
Summary: The prevalence of peripartum depression in women with multiple sclerosis appears to be similar to the general population, with factors such as older age, primiparity, pre-pregnancy depression, sleep disturbance, and breastfeeding difficulty associated with higher risk. Prospective studies are needed to further explore the impact of peripartum depression on self-management in multiple sclerosis and offspring development.
MULTIPLE SCLEROSIS JOURNAL
(2022)
Article
Clinical Neurology
Marco Pisa, Jonathan Pansieri, Sydney Yee, Jennifer Ruiz, Isabel M. Leite, Jacqueline Palace, Giancarlo Comi, Margaret M. Esiri, Letizia Leocani, Gabriele C. DeLuca
Summary: The anterior optic pathway is often affected in CNS inflammatory demyelinating diseases, with optic neuritis as a common symptom. However, optic nerve involvement can also be subclinical. This study investigates the pathological basis of these findings and shows that chronic inflammation leads to neurodegeneration in multiple sclerosis and neuromyelitis optica.
Article
Clinical Neurology
Richard L. Yates, Jonathan Pansieri, Qizhu Li, Jack S. Bell, Sydney A. Yee, Jacqueline Palace, Margaret M. Esiri, Gabriele C. DeLuca
Summary: The study found that the HLA-DRB1*15 genotype is associated with the relationship between cortical inflammation and neuronal density in multiple sclerosis, suggesting a potential modulation effect of HLA-DRB1*15 on these factors.
Review
Clinical Neurology
Gina Hadley, Jiali Zhang, Eva Harris-Skillman, Zoi Alexopoulou, Gabriele C. DeLuca, Sarah T. Pendlebury
Summary: Based on a systematic review of the literature, we determined the relative contributions of different neuropathologies to the excess risk of cognitive decline in diabetes mellitus (DM). The findings showed no association between DM and Alzheimer's disease (AD)-related neuropathology, but an association with increased large and small vessel disease. Additional studies are needed to further evaluate the relative contributions of different neuropathologies to the excess risk of DM.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Article
Clinical Neurology
Jonathan I. Spencer, Maximillian Crane, Marco Pisa, Alex D. Waldman, Gabriele C. DeLuca
Summary: The global tally of neurological disorders is rising, and research into novel therapies is needed. Plasma exchange, traditionally used for antibody-mediated neurological diseases, may have wider potential uses by removing neurotoxic proteins.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2022)
Review
Clinical Neurology
Winston M. Zhu, Ain Neuhaus, Daniel J. Beard, Brad A. Sutherland, Gabriele C. DeLuca
Summary: To meet the metabolic demands of the brain, mechanisms have evolved to couple neuronal activity to vasodilation, increasing cerebral blood flow. The release of vasoactive molecules by neurons and astrocytes plays a key role in signaling pathways that induce vasodilation. Understanding neurovascular coupling is especially important in Alzheimer's disease, where disrupted cerebral blood flow regulation is a prominent feature.
Article
Clinical Neurology
Marco Pisa, Jennifer A. Ruiz, Gabriele C. DeLuca, Marta de Andres Crespo, Heather M. DelMastro, Kayla M. Olson, Elizabeth W. Triche, Albert C. Lo
Summary: Dysfunction in upper limb function is common in persons with multiple sclerosis, even in those with mild disability. Box and Block Test (BBT), finger-nose test (FNT), and Nine-Hole Peg Test (NHPT) have been identified as the most accurate measures to detect upper limb dysfunction.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2022)
Article
Neurosciences
Max Kaufmann, Anna-Lena Schaupp, Rosa Sun, Fabian Coscia, Calliope A. Dendrou, Adrian Cortes, Gurman Kaur, Hayley G. Evans, Annelie Mollbrink, Jose Fernandez Navarro, Jana K. Sonner, Christina Mayer, Gabriele C. DeLuca, Joakim Lundeberg, Paul M. Matthews, Kathrine E. Attfield, Manuel A. Friese, Matthias Mann, Lars Fugger
Summary: This study identified multicellular mechanisms of progressive multiple sclerosis (MS) pathogenesis and traced their origin in relation to spatially distributed stages of neurodegeneration by using spatial transcriptomics and proteomics. Defunct trophic and anti-inflammatory intercellular communications were discovered within areas of early neuronal decline in MS patients. Proteins associated with neuronal damage in patient samples showed mechanistic concordance with in vivo knockdown and central nervous system (CNS) disease models. This study provides a new framework for drug development strategies and uncovers new therapeutic opportunities to slow disease.
NATURE NEUROSCIENCE
(2022)
Article
Clinical Neurology
Ruth Dobson, Matthew Craner, Ed Ed Waddingham, Aleisha Miller, Jayant Pindoria, Ana Cavey, Camilla Blain, Gabriele De Luca, Nikos Evangelou, Helen Ford, Paul Gallagher, Katila George, Ruth Geraldes Ramos Dias, Paula Harman, Jeremy Hobart, Tanya King, Ruth Linighan, Niall MacDougall, Monica Marta, Stephanie Mitchell, Richard Nicholas, David Rog, Antonio Scalfari, Neil Scolding, Stewart Webb, Sarah White, Judith Wilton, Carolyn Young, Paul Matthews
Summary: This study analyzed the risk of adverse events in multiple sclerosis (MS) patients receiving disease-modifying therapies (DMTs) through an observational study. It found that certain DMTs had a higher incidence of adverse events. This highlights the potential of routinely collected healthcare data to evaluate the safety of DMTs in real-world clinical practice.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2022)
Article
Clinical Neurology
Dessa Sadovnick, Maria Criscuoli, Irene Yee, Robert Carruthers, Alice Schabas, Virginia Devonshire, Penelope Smyth
Summary: This study found that women with multiple sclerosis (MS) do not have a higher risk of first-trimester miscarriages compared to the general population.
MULTIPLE SCLEROSIS JOURNAL
(2023)
Article
Clinical Neurology
Bridget LaMonica Ostrem, Annika Anderson, Sarah Conway, Brian C. Healy, Jiwon Oh, Dina Jacobs, Ruth Dobson, Edith Larmon Graham, A. Dessa Sadovnick, Vanessa Zimmerman, Yanqing Liu, Riley Bove, Maria Houtchens
Summary: Moderately to severely disabled women with MS have a lower risk of relapse during pregnancy, but a significant increase postpartum. Women with higher preconception EDSS have a greater risk of relapses and disability worsening postpartum.
MULTIPLE SCLEROSIS JOURNAL-EXPERIMENTAL TRANSLATIONAL AND CLINICAL
(2022)
Article
Clinical Neurology
Dessa Sadovnick, Maria Criscuoli, Irene Yee, Robert Carruthers, Alice Schabas, Penelope Smyth
Summary: This prospective real world study aims to gain insight into the various paths to conception that women with MS take, including the use of assisted reproductive technologies and decisions regarding disease modifying therapy. The study highlights the lack of international consensus on managing these women and the importance of providing real world data through studies like CANPREG-MS.
MULTIPLE SCLEROSIS JOURNAL-EXPERIMENTAL TRANSLATIONAL AND CLINICAL
(2021)
