The umpteenth study on causality means very little if it is not scientifically plausible. This is core science, and it’s what real scientists work on.
EBV infection has long been strong contender for the development of MS. But, how strong is this link? What does having had EBV as a teenager do to your biological makeup (i.e. endophenotype)?
In a first study of its kind the Swedish group examined the CSF from healthy non-MS individuals with previous history of of infectious mononucleosis (EBV infection) approximately 10 years after the event. They compared this with untreated individuals with MS and healthy controls.
The sample size was limited, but they did find elevated levels of CSF IP-10, YKL-40 and CCL-2 inflammatory markers in controls vs. previous history of infectious mononucleosis (see figure below). Moreover, the average levels of all 7 inflammatory markers that were tested did show a trend towards higher levels in the post-infectious mononucleosis group but this was not statistically significant. Therefore, this study failed establish a step-wise infectious mononucleosis – MS association at the biological level. However, a larger study may find differently. What is certain is that having an MS associated endophenotype is not enough to develop the disease itself.
This type of science is a minefield of suppositions, like for instance what is a sufficient interval to come back and check an individual in the future (is 10 years sufficient?), and how near or far is a certain MS endophenotype to fully developed pre-MS (I’m not talking about MS, which again is slightly different)?
Acta Neurol Scand. 2020 May 16. doi: 10.1111/ane.13280. [Epub ahead of print]
Intrathecal immunoreactivity in people with or without previous infectious mononucleosis.
The risk of developing multiple sclerosis (MS) increases (OR: 3.1) after infectious mononucleosis (IM). However, the nature of this link is obscure. We tested the hypothesis that IM might incur long-term sequelae, including low-key inflammatory activity, with characteristics of an MS endophenotype (or presymptomatic trait), and that assays of MS-relevant cyto-/chemokines in the cerebrospinal fluid (CSF) post IM may show a trend in this direction.
MATERIALS AND METHODS:
We selected seven CSF cytokines (IL-1b, IL-6, YKL-40, TNF-alpha) or chemokines (IL-8, CCL2, IP-10), representing pro-inflammatory factors previously associated with MS. We assayed the CSF levels of these seven cyto-/chemokines in healthy individuals with a median follow-up time of 10 years after serologically confirmed IM (post-IM group, n=22), and in healthy controls without a history of IM (n=19). A group of MS patients (n=23) were included as reference.
The CSF levels of IP-10, YKL-40 and CCL-2 were higher in the post-IM group than in our IM unexposed controls (p = 0.021, 0.049, 0.028). Seven of seven cyto/chemokine assays showed a trend in the predicted direction (p of binomial ratio = 0.008). However, this trend was non-significant in a multivariate test (p = 0.22). A power analysis indicated that similar studies including a larger cohort would be numerically realistic.
These results do not reject the hypothesis that the established epidemiological association between IM and MS results from a stepwise inflammatory propagation from IM sequele to an MS endophenotype (or presymptomatic trait) in a proportion of IM patients, pending confirmation with adequate power.