The concentrations of antibodies to Epstein-Barr virus decrease during ocrelizumab treatment

H Phuong T Pham; Sepideh Saroukhani; J William Lindsey

doi:10.1016/j.msard.2023.104497

The concentrations of antibodies to Epstein-Barr virus decrease during ocrelizumab treatment

Mult Scler Relat Disord. 2023 Feb:70:104497. doi: 10.1016/j.msard.2023.104497. Epub 2023 Jan 2.

Authors

H Phuong T Pham¹, Sepideh Saroukhani², J William Lindsey³

Affiliations

¹ Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA.
² Division of Clinical and Translational Sciences, Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA; Biostatistics/Epidemiology/Research Design (BERD) component, Center for Clinical and Translational Sciences (CCTS), The University of Texas Health Science Center at Houston, Houston, Texas, USA.
³ Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA. Electronic address: john.w.lindsey@uth.tmc.edu.

PMID: 36603289
DOI: 10.1016/j.msard.2023.104497

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: B cell depletion; Epstein-Barr virus; Multiple sclerosis; Ocrelizumab; antibody response.

MeSH terms

Antibodies, Viral
Epstein-Barr Virus Infections* / complications
Epstein-Barr Virus Nuclear Antigens
Herpesvirus 4, Human
Humans
Multiple Sclerosis* / complications
Septins

Substances

ocrelizumab
Septins
Antibodies, Viral
Epstein-Barr Virus Nuclear Antigens