Highlights
- •Antibodies to two major Epstein-Barr virus antigens, EBNA-1 and BFRF3, decrease in people treated with ocrevus.
- •Antibodies to two human proteins known to cross-react with Epstein-Barr virus had a trend towards decreasing on ocrevus treatment.
- •A treatment that removed only Epstein-Barr virus infected B lymphocytes might be effective and have less side effects.
Abstract
Background
Epstein‐Barr Virus (EBV) is strongly associated with multiple sclerosis (MS). After
initial infection, EBV maintains a life‐long latent infection in B lymphocytes. Depletion
of B lymphocytes from the blood with the anti-CD20 antibody ocrelizumab (OCR) markedly
reduces disease activity in MS. Our objective was to measure the effect of OCR treatment
on the antibody response to EBV and human antigens that are cross-reactive with EBV.
Methods
Blood was collected from MS patients before and during OCR treatment. Antibodies to
three EBV antigens (EBNA-1, BFRF3, and gp350) and three human proteins that are cross-reactive
with EBV (septin-9, DLST, and HNRNPL) were quantified with Western blots. Antibodies
to EBNA-1 and BFRF3 were also quantified with ELISA.
Results
Antibodies to the EBV proteins BFRF3 and EBNA-1 measured on Western blot were significantly
decreased after 12 months on OCR. Subsequent testing with ELISA confirmed the decrease
for both BFRF3 and EBNA-1. With Western blots, there was a trend to decreased antibody
response to septin-9 and DLST, but not HNRNPL. Total IgG concentration did not change.
Conclusion
The antibody response to some EBV antigens decreases in OCR treated patients. The
benefit of OCR for MS may be through removal of EBV antigenic stimulus.
Keywords
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References
- Duration of humoral immunity to common viral and vaccine antigens.N. Engl. J. Med. 2007; 357: 1903-1915
- Epstein-Barr virus in multiple sclerosis: theory and emerging immunotherapies.Trends Mol. Med. 2020; 26: 296-310
- The elimination of circulating Epstein-Barr virus infected B cells underlies anti-CD20 monoclonal antibody activity in multiple sclerosis: a hypothesis.Mult. Scler. Relat. Disord. 2022; 59103678
- The increased antibody response to Epstein-Barr virus in multiple sclerosis is restricted to selected virus proteins.J. Neuroimmunol. 2016; 299: 147-151
- Ocrelizumab versus interferon Beta-1A in relapsing multiple sclerosis.N. Engl. J. Med. 2017; 376: 221-234
- Antibodies to the Epstein-Barr virus proteins BFRF3 and BRRF2 cross-react with human proteins.J. Neuroimmunol. 2017; 310: 131-134
- Antibodies specific for Epstein-Barr virus nuclear antigen-1 cross-react with human heterogeneous nuclear ribonucleoprotein L.Mol. Immunol. 2016; 69: 7-12
- The antibody response to Epstein-Barr virions is altered in multiple sclerosis.J. Neuroimmunol. 2013; 254: 146-153
- The cellular immune response against Epstein-Barr virus decreases during ocrelizumab treatment.Mult. Scler. Relat. Disord. 2021; 56103282
- Role of Th17 cells in the pathogenesis of CNS inflammatory demyelination.J. Neurol. Sci. 2013; 333: 76-87
- The role of Epstein-Barr virus in the etiology of multiple sclerosis: a current review.Expert Rev. Clin. Immunol. 2020; 16: 1143-1157
- T helper 17.1 cells associate with multiple sclerosis disease activity: perspectives for early intervention.Brain. 2018; 141: 1334-1349
- Multiple sclerosis is an inflammatory T-cell-mediated autoimmune disease.Arch. Neurol. 2004; 61: 1613-1615
- Effect of ocrelizumab on leptomeningeal inflammation and humoral response to Epstein-Barr virus in multiple sclerosis. A pilot study.Mult. Scler. Relat. Disord. 2022; 67104094
Article info
Publication history
Published online: January 02, 2023
Accepted:
January 1,
2023
Received in revised form:
December 4,
2022
Received:
October 20,
2022
Identification
Copyright
© 2023 Elsevier B.V. All rights reserved.
