Current and past EBV infection in CIS

Objectives: To assess risk of a first clinical diagnosis of clinically isolated syndrome (CIS) in relation to measures of Epstein-Barr virus (EBV) infection within the context of other known risk factors.
Results: Higher anti-EBV antibody levels and a history of infectious mononucleosis (IM) were associated with increased CIS  risk and there was an additive interaction with the main MS susceptibility gene HLA-DRB1*1501. There were additional interactions between high anti-EBNA antibody levels and variants in the HLA-A gene; if yo had both of these factors or your risk of CIS was 20X greater than if you had neither of these factors. EBV viral load was lower at higher serum vitamin D concentrations in controls subjects. 
Conclusion: Past infection with EBV, but not current EBV viral load in whole blood, is significantly associated with increased CIS risk. These associations are modified by immune-related gene variants.
“Yet another study showing an interaction between EBV and the immune function gene associated with increased MS risk. The risk of getting CIS if you have both risk factors is 20x greater than if you don’t. Interesting?”

“This study also hints at an interaction between EBV and vitamin D levels; this is not surprising given the major role vitamin D plays in immune function.”

“Another bit of evidence supporting the need to do large studies to try and bring the MS risk factors together in a prediction study. We are hoping to do this with our PredictMS study.”

“This study also supports the need to be vitamin D replete.”
Additional reading: Vitamin D, HLA, EBV

6 thoughts on “Current and past EBV infection in CIS”

  1. "Yet another study showing an interaction between EBV and the immune function gene associated with increased MS risk. The risk of getting CIS if you have both risk factors is 20x greater than if you don't. Interesting?"This is an angry post – so advanced warning.I've lost count of the number of MS research papers which show a link between MS and EBV infection. This week there has been two. Most reach the same conclusion – association between EBV infection and getting MS. Why do they never progress beyond this? They hint at a connection / EBV being the potential cause, but never actually make any bold conclusion. The evidence has been mounting over the past couple of decades, but I don't know of any trials which are looking at anti-virals. I can see that in 2020, there will still be research papers noting that "there appears to be a strong link between getting infected with EBV and getting MS". I think you say that your team will put in an application for a trial using an anti-viral treatment. To quote Nike – "Just do it". Any more EBV / MS researcher papers in the near future making the same old observation will push me over the edge.Angry of Tunbridge Wells.

  2. Re "Just do it". We would love to just do it. We had our grant to the Wellcome Trust on an EBV anti-viral study turned down despite a favourable peer-review. We are about to resubmit a grant application to the MRC to do the study. Unfortunately, research particularly clinical trials cost a lot and need resource (staff) to do them. We will get there. Finally, I believe Rituximab and Ocrelizumab, drugs that target B-cells are anti-EBV. The phase 2 results from them look stunning. There are two trials recruiting for Ocrelizumab a RRMS and a PPMS trial. Please watch this space.

  3. Prof G,Apologies – my "just do it" was aimed at the whole system (researchers and funders). Good ideas really get stuck in the swamp – I'm guessing an anti-viral approach is of no interest to big pharma. With regard to Rituximab and Ocrelizumab, in what way are the results stunning? Are they targetted at reducing relapses or progression (or both)? Is one superior over the other?

  4. Re: "Rituximab and Ocrelizumab"The phase 2 results are probably the best reported, apart from Alemtuzumab, of all the DMTs. What is interesting is that Rituximab is the only licensed anti-EBV drug. It is used to treat a rare disease due to EBV that typically occurs in subjects after bone marrow transplantation. The disorder is called EBV-associated lymphoproliferative disorder. In this disorder Rituximab causes EBV levels to plummet. Not sure which one is better; ocrelizumab is the daughter of Rituximab. With regard to treating progressive disease there is a whole series of posts on this blog covering the issue of B cells and B cell follicles being the drivers of progression. The good news is that ocrelizumab is being tested in PPMS so we will get a definitive answer on how good it is in progressive MS. Unfortunately, the trial is only recruiting now so the results will only be available in about 5 years.

  5. Re: "If it's true that Biogen is pursuing ocrelizumab because Rituximab will be off patent then there's something very wrong with the system."It is not Biogen, but Roche/Genentech. Under their agreement they share 50:50 on Rituximab and only 25:75 with Ocrelizumab. In addition, Rituximab is already on the market at a fixed price, at least in Europe. Ocrelizumab, will almost certainly cost more. At the end of the day Pharma is a business; they are not necessarily in the game for MS'ers.

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