Complete Epstein-Barr virus seropositivity in a large cohort of patients with early multiple sclerosis

Abrahamyan, Sargis; Eberspächer, Bettina; Hoshi, Muna-Miriam; Aly, Lilian; Luessi, Felix; Groppa, Sergiu; Klotz, Luisa; Meuth, Sven G.; Schroeder, Christoph; Grüter, Thomas; Tackenberg, Björn; Paul, Friedemann; Then-Bergh, Florian; Kümpfel, Tania; Weber, Frank; Stangel, Martin; Bayas, Antonios; Wildemann, Brigitte; Heesen, Christoph; Zettl, Uwe K.; Warnke, Clemens; Antony, Gisela; Heßler, Nicole; Wiendl, Heinz; Bittner, Stefan; Hemmer, Bernhard; Gold, Ralf; Salmen, Anke; Ruprecht, Klemens

doi:10.1136/jnnp-2020-322941

Cited by 76 publications

(79 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The serum of all individuals with CIS or MS contained anti-EBV EBNA-1 IgG antibodies at a titre of 1:32 or greater indicating chronic EBV infection, as expected ( 44 ). In addition, the serum of 8/22 (36%) people with CIS or MS also contained anti-EBV VCA IgM antibodies, which is considerably higher than the 3–6% rate of seropositivity demonstrated in other clinical settings ( 45 ).…”

Section: Resultssupporting

confidence: 73%

FcγRIIb Expression Is Decreased on Naive and Marginal Zone-Like B Cells From Females With Multiple Sclerosis

et al. 2021

View full text Add to dashboard Cite

B cells are critical to the development of multiple sclerosis (MS), but the mechanisms by which they contribute to the disease are poorly defined. We hypothesised that the expression of CD32b (FcγRIIb), a receptor for the Fc region of IgG with inhibitory activities in B cells, is lower on B cell subsets from people with clinically isolated syndrome (CIS) or MS. CD32b expression was highest on post-naive IgM+ B cell subsets in healthy controls. For females with MS or CIS, significantly lower CD32b expression was identified on IgM+ B cell subsets, including naive and IgMhi MZ-like B cells, when compared with control females. Lower CD32b expression on these B cell subsets was associated with detectable anti-Epstein Barr Virus viral capsid antigen IgM antibodies, and higher serum levels of B cell activating factor. To investigate the effects of lower CD32b expression, B cells were polyclonally activated in the presence of IgG immune complexes, with or without a CD32b blocking antibody, and the expression of TNF and IL-10 in B cell subsets was assessed. The reduction of TNF but not IL-10 expression in controls mediated by IgG immune complexes was reversed by CD32b blockade in naive and IgMhi MZ-like B cells only. However, no consequence of lower CD32b expression on these cells from females with CIS or MS was detected. Our findings highlight a potential role for naive and marginal zone-like B cells in the immunopathogenesis of MS in females, which requires further investigation.

show abstract

Section: Resultssupporting

confidence: 73%

FcγRIIb Expression Is Decreased on Naive and Marginal Zone-Like B Cells From Females With Multiple Sclerosis

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Another virus implicated in MS pathogenesis is the Epstein–Barr virus (EBV), a member of the herpes virus family that causes infectious mononucleosis [ 66 , 67 ]. While more than 95% of healthy individuals demonstrate an immune response to EBV, virtually all MS patients are seropositive for EBV [ 68 , 69 ]. Libbey et al [ 70 ] hypothesize that MS could be triggered via molecular mimicry, whereby specific peptides secreted by pathogens have sequence or structural similarities to self-antigens.…”

Section: Immune Activation: What Is the Motive For The Crime?mentioning

confidence: 99%

The Nerves to Conduct a Multiple Sclerosis Crime Investigation

Chopra

Myers

Sekhon

et al. 2021

IJMS

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative autoimmune disease characterized by the aberrant infiltration of immune cells into the central nervous system (CNS) and by the loss of myelin. Sclerotic lesions and various inhibitory factors hamper the remyelination processes within the CNS. MS patients typically experience gradual cognitive and physical disabilities as the disease progresses. The etiology of MS is still unclear and emerging evidence suggests that microbiome composition could play a much more significant role in disease pathogenesis than was initially thought. Initially believed to be isolated to the gut microenvironment, we now know that the microbiome plays a much broader role in various tissues and is essential in the development of the immune system. Here, we present some of the unexpected roles that the microbiome plays in MS and discuss approaches for the development of next-generation treatment strategies.

show abstract

“…Although the primary cause of MS is unknown, genetic and environmental factors contribute to the risk of developing MS. A mounting body of evidence indicates that infection with Epstein–Barr virus (EBV) has an important role in the pathogenesis of MS ( 1 , 2 ). In particular, the universality of EBV infection in people with MS ( 3 ) including those with early MS ( 4 ), and the presence of high titres of anti-EBV antibodies in the sera of patients prior to the onset of MS ( 5 – 8 ) and during the course of MS ( 9 ) indicate that infection with EBV has a critical role in the development of MS.…”

Section: Introductionmentioning

confidence: 99%

Sustained Clinical Improvement in a Subset of Patients With Progressive Multiple Sclerosis Treated With Epstein–Barr Virus-Specific T Cell Therapy

et al. 2021

View full text Add to dashboard Cite

Background: Increasing evidence indicates a role for Epstein–Barr virus (EBV) in the pathogenesis of multiple sclerosis (MS). EBV-infected autoreactive B cells might accumulate in the central nervous system because of defective cytotoxic CD8+ T cell immunity. We have previously reported results of a phase I clinical trial of autologous EBV-specific T cell therapy in MS 6 months after treatment.Objective: To investigate longer-term outcomes in MS patients who received autologous EBV-specific T cell therapy.Methods: We assessed participants 2 and 3 years after completion of T cell therapy.Results: We collected data from all 10 treated participants at year 2 and from 9 participants at year 3. No serious treatment-related adverse events were observed. Four participants had at least some sustained clinical improvement at year 2, including reduced fatigue in three participants, and reduced Expanded Disability Status Scale score in two participants. Three participants experienced a sustained improvement in at least some symptoms at year 3. More sustained improvement was associated with higher EBV-specific CD8+ T cell reactivity in the administered T cell product.Conclusion: Autologous EBV-specific T cell therapy is well-tolerated, and some degree of clinical improvement can be sustained for up to 3 years after treatment.

show abstract

Complete Epstein-Barr virus seropositivity in a large cohort of patients with early multiple sclerosis

Cited by 76 publications

References 25 publications

FcγRIIb Expression Is Decreased on Naive and Marginal Zone-Like B Cells From Females With Multiple Sclerosis

FcγRIIb Expression Is Decreased on Naive and Marginal Zone-Like B Cells From Females With Multiple Sclerosis

The Nerves to Conduct a Multiple Sclerosis Crime Investigation

Sustained Clinical Improvement in a Subset of Patients With Progressive Multiple Sclerosis Treated With Epstein–Barr Virus-Specific T Cell Therapy

Contact Info

Product

Resources

About