A few weeks ago, our MS journal club looked at a couple of papers exploring how EBV relapses in MS. This question interested me, and the rest of the group I think, for two reasons:

First, scientific curiosity, if there’s one positive from my MS diagnosis (this really is scraping the barrel), it’s that this is an exciting area of scientific research and learning about all of the molecular mechanisms, immunology, physiology etc is really invigorating.

Second, once we know why, after a period of blessed dormancy, our immune system has another go at the myelin round our nerves, the more chance there is of a cure (see below, but SPOILER: don’t get your hopes up yet).

As I noted in the teaser post for the club’s topic this time, there are two main theories:

  • the older hit and run theory – ie that EBV triggers the immune system which then continues to attack myelin, mistaking it for the virus
  • the viral reactivation theory – ie that that EBV lies latent in B-cells, but keeps emerging and reactivating the immune system, thus causing relapses. 

Gavin Giovannoni, as you might expect, does a good job of summarising both theories so I’m not going to do much more than post the powerpoint on the viral reactivation theory that one of our number (who would like to remain anonymous) prepared for the group.

I then spotted a third paper rush past on Twitter which was readable and provided a different route into understanding the reactivation theory.

Soldan and Lieberman (2022) Epstein–Barr virus and multiple sclerosis, Nature Reviews Microbiology

It’s really worth noting I think, that this paper is much less positive about the potential for a vaccine to reduce or prevent relapses.

“There are distinct challenges for EBV vaccine development. Sterilizing immunity to EBV may not be possible given the efficiency of EBV transmission and persistence, and merely delaying the time of infection is undesirable, because it increases the risk of mononucleosis and MS…” (p10).

This paper is therefore more cautious than the main paper we read, and Gavin Giovannoni, about the potential that a vaccine against EBV could stop relapses by clearing it from the B-Cells it lies dormant. This will be difficult to do and there is evidence of a genetic component to the way this latency works that means not everyone will benefit (beware, this is a lay person’s reading of the paper that may have got the wrong end of the stick).

The second part of that quote holds out a different risk. There is evidence that people who catch EBV when very young don’t go on to have MS. But those who catch it in their teens or later are much more at risk of glandular fever (monnucleosis) and MS. So vaccinating children against EBV might mean more people suffer from MS. We need to proceed with vaccination cautiously (but we need to proceed, don’t take this negative take as suggesting we shouldn’t, just let’s not be starry eyed).

Now that the club has looked at the heritability of MS, and the role of the gut microbiome in MS, I’m increasingly struck by how complex and individual the causes and responses to therapy are. I’m confident that cures will emerge, but I’m now inoculated (to about 80% effectiveness) against people getting exciting about a cure being just round the corner. I think this realistic position is probably a good position to be in as it’s better for my mental health.