Ocrelizumab B cell depletion has no effect on HERV RNA expression in PBMC in MS patients

Tarlinton, Rachael; Tanasescu, Radu; Shannon-Lowe, Claire; Gran, Bruno

Abstract

Background
Epstein barr virus (EBV) infection of B cells is now understood to be one of the triggering events for the development of Multiple Sclerosis (MS), a progressive immune-mediated disease of the central nervous system. EBV infection is also linked to expression of human endogenous retroviruses (HERVs) of the HERV-W group, a further risk factor for the development of MS. Ocrelizumab is a high-potency disease-modifying treatment (DMT) for MS, which depletes B cells by targeting CD20.

Objectives
We studied the effects of ocrelizumab on gene expression in peripheral blood mononuclear cells (PBMC) from paired samples from 20 patients taken prior to and 6 months after beginning ocrelizumab therapy. We hypothesised that EBV and HERV-W loads would be lower in post-treatment samples.

Methods
Samples were collected in Paxgene tubes, subject to RNA extraction and Illumina paired end short read mRNA sequencing with mapping of sequence reads to the human genome using Salmon and differential gene expression compared with DeSeq2. Mapping was also performed separately to the HERV-D database of HERV sequences and the EBV reference sequence.

Results
Patient samples were more strongly clustered by individual rather than disease type (relapsing/remitting or primary progressive), treatment (pre and post), age, or sex. Fourteen genes, all clearly linked to B cell function were significantly down regulated in the post treatment samples. Interestingly only one pre-treatment sample had detectable EBV RNA and there were no significant differences in HERV expression (of any group) between pre- and post-treatment samples.

Conclusions
While EBV and HERV expression are clearly linked to triggering MS pathogenesis, it does not appear that high level expression of these viruses is a part of the ongoing disease process or that changes in virus load are associated with ocrelizumab treatment.

Citation

Tarlinton, R., Tanasescu, R., Shannon-Lowe, C., & Gran, B. (2024). Ocrelizumab B cell depletion has no effect on HERV RNA expression in PBMC in MS patients. Multiple Sclerosis and Related Disorders, 86, Article 105597. https://doi.org/10.1016/j.msard.2024.105597

• Journal Article Type: Article
• Acceptance Date: Mar 29, 2024
• Online Publication Date: Mar 30, 2024
• Publication Date: 2024-06
• Deposit Date: Jun 15, 2024
• Publicly Available Date: Jun 18, 2024
• Journal: Multiple Sclerosis and Related Disorders
• Print ISSN: 2211-0348
• Electronic ISSN: 2211-0356
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 86
• Article Number: 105597
• DOI: https://doi.org/10.1016/j.msard.2024.105597
• Keywords: Multiple sclerosis; Ocrelizumab; Epstein barr virus; Human Endogenous Retrovirus
• Public URL: https://nottingham-repository.worktribe.com/output/33549038
• Publisher URL: https://www.msard-journal.com/article/S2211-0348(24)00176-7/fulltext
• Additional Information: This article is maintained by: Elsevier; Article Title: Ocrelizumab B cell depletion has no effect on HERV RNA expression in PBMC in MS patients; Journal Title: Multiple Sclerosis and Related Disorders; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.msard.2024.105597; Content Type: article; Copyright: © 2024 The Authors. Published by Elsevier B.V.