This Is MS Multiple Sclerosis Knowledge & Support Community

What are T-cells telling us about how EBV causes MS?

https://www.msard-journal.com/article/S ... 5/fulltext

Abstract

As reviewed by others (Robinson and Steinman, 2022; Sollid, 2022); (Giovannoni et al., 2022b; Läderach and Münz, 2022); ( Maple et al., 2022) and in our prior Editors' commentary (Giovannoni et al., 2022a), the evidence that EBV plays a pivotal role in the causal pathway that leads to MS is now overwhelming. Currently, there are two main competing theories of how EBV causes MS.

On the one hand, is the ‘hit-and-run’ theory that EBV triggers autoimmunity through molecular mimicry, i.e. EBV fools the immune system into making an immune reaction against its proteins/antigens, in particular, EBV nuclear antigen-1 (EBNA-1), which then cross-reacts with antigens in the central nervous system (CNS) to cause focal inflammatory events that is MS (Läderach and Münz, 2022).

A second theory is that EBV is the ‘driver of MS’ by continually cycling through its latent and lytic infection phases is responsible for driving MS pathology (Giovannoni et al., 2022b). This could either be by (1) direct CNS infection, (2) continuously stimulating autoreactive T and B cells, or (3) upregulating a second virus such as MS-associated HERVs (human endogenous retroviruses or human herpes virus 6), which in turn cause tissue damage (Küry et al., 2018).

This latter is called the ‘dual-viral’ hypothesis of MS (Giovannoni et al., 2007).

Increase in Epstein Barr virus serologies precedes neuroaxonal damage in pre-symptomatic multiple sclerosis

https://www.diva-portal.org/smash/recor ... dswid=1653

Introduction: Epstein-Barr virus (EBV) infection may be a pre-condition for the development of multiple sclerosis (MS). EBV antibodies, predominantly anti-EBNA1, develop in the presymptomatic phase of virtually all MS patients. Using material from a serum repository, studies in advance of MS onset indicated that EBV seropositivity preceded the first expression of incipient axonal lesions, serum Neurofilament Light (sNFL) .

Objectives: To determine the onset and individual order of appearance of EBV seroreactivity and the serum neuroaxonal injury marker neurofilament light (sNfL) in a wide age spectrum of presymptomatic MS patients.

Aims: To characterize the presymptomatic appearance of anti-bodies against an intranuclear (EBNA1) and a surface EBV anti-gen (gp350) and sNfL.

Methods: A nested case-control study in 669 pre-symptomatically acquired blood samples from persons who later received an MS diagnosis, and from 1:1 matched control persons. Serum levels of EBNA1, VCA and gp350 IgG antibodies and sNFL (n=519) were measured in individual presymptomatic samples and expressed as delta scores with matched controls in relation to time until MS onset.

Results: Serum levels expressed as delta scores for anti EBV and NfL IgG showed an incipient increase for anti EBNA1 and gp350 from 15-20 years before MS debut. Significant (p=0.001 and p=0.002) from 10-15 years, with consistent delta-scores successively closer to MS onset. These findings contrasted to the level of sNfL which increasingly diverged from matched controls from 5-10 years before the onset of MS. None of the individual samples negative for both EBNA1 and VCA IgG antibodies in the pre-MS group (n = 36) showed any elevation of the sNfL level.

Conclusions: In a pre-MS material, the seroreactivity against EBNA1 was followed by VCA and gp350, before increased sNFL appeared, indicating incipient axonal injury. Together with its biological characteristics this temporal order confirms the role of EBV as a trigger of MS.