Summary: This post sets the scene for revisiting the Bradford-Hill criteria around EBV being the cause of MS.
Are we any closer to proving EBV is the cause of MS? I have posted on this topic many times before, but one of the Bradford-Hill criteria we use for establishing causation is ‘Coherence with Biological Background and Previous Knowledge’. We now have at least nine classes of DMTs that have been shown to work in MS. Over the last few months, we have been making the case that they work via B-cells in particular memory B-cells. It may be a coincidence that the memory B cell is the main cell where EBV resides in a latent state. The challenge now is how to work this knowledge into what we know about the pathogenesis of MS and the other factors that are in the causal pathway, for example, smoking, vD and UVB sunlight exposure, female sex and the genetic pathways identified from the whole genome association studies. We have so much to do and so little time. Regardless of this work, we need to start our proposed infectious mononucleosis and EBV vaccination studies sooner than later. Causation will only be proved when we show that preventing, or treating infectious mononucleosis or preventing EBV infection reduces the incidence of MS.
The British Statistician, Sir Austin Bradford-Hill, has formulated more general and appropriate criteria of causation; the following are the Bradford-Hill criteria:
1. CONSISTENCY AND UNBIASEDNESS OF FINDINGS
2. STRENGTH OF ASSOCIATION
3. TEMPORAL SEQUENCE
4. BIOLOGICAL GRADIENT (DOSE-RESPONSE RELATIONSHIP)
6. COHERENCE WITH BIOLOGICAL BACKGROUND AND PREVIOUS KNOWLEDGE
7. BIOLOGICAL PLAUSIBILITY
8. REASONING BY ANALOGY
9. EXPERIMENTAL EVIDENCE
If you are interested in reading about these criteria I suggest the following references:
Bradford-Hill’s criteria have been modified to apply them to the problem of MS. I coauthored the following paper over 10 years ago. I think it is time to update it with new knowledge that has been acquired since then. The case now is more compelling than ever.
CoI: multiple and I am convinced EBV is the cause of MS.