Premission to reproduce from Prof. G Endogeneous viral genes are associated with MS susceptibility The black swan is circling; when will it land? "The study below links genetic markers close to where a member of the human endogenous retroviruses resides in our genomes with MS susceptibility and MS severity. Rule one with these types of studies is to ask others to reproduce the result. This could easily be done using data from the International MS Genetics Consortium. The odds are it won't be reproduced; only 5% of studies like this get reproduced." "If the results are reproduced this would be very interesting indeed and would pose a long list of questions about whether or not these genetic variants have biological effects and how we can link these effects to MS biology. The authors discuss some speculative ideas around this theme in their discussion." "As you can see this virus resides on the X, or female chromosome, hence females have two copies. Whether or not this has any relevance to the female preponderance of MS is also of interest." "The good news about this paper is that another reasearch group is exploring the link, or putative link, between MS and viruses, in this case a specific HERV. Let's hope their hypotheses lead us closer to the cause of MS. It always takes out-of-the-box thinking to change the paradigm. We need to keep an open mind about alternative explanations about the pathogenesis of MS; particularly since the autoimmune dogma has many holes and inconsistencies in it." "Is their a black swan circling? For those of you interested in the black swan analogy should read my previous post on this topic: click here." Epub: García-Montojo et al. HERV-W polymorphism in chromosome X is associated with multiple sclerosis risk and with differential expression of MSRV. Retrovirology. 2014;11(1):2. BACKGROUND: MS is an autoimmune demyelinating disease that occurs more frequently in women than in men. MS Associated Retrovirus (MSRV) is a member of HERV-W, a multicopy human endogenous retroviral family repeatedly implicated in MS pathogenesis. MSRV envelope protein is elevated in the serum of MSers and induces inflammation and demyelination but, in spite of this pathogenic potential, its exact genomic origin and mechanism of generation are unknown. A possible link between the HERV-W copy on chromosome Xq22.3, that contains an almost complete open reading frame, and the gender differential prevalence in MS has been suggested. RESULTS: MSRV transcription levels were higher in MSers than in controls (U-Mann-Whitney; p = 0.004). Also, they were associated with the clinical forms (Spearman; p = 0.0003) and with the Multiple Sclerosis Severity Score (MSSS) (Spearman; p = 0.016). By mapping a 3 kb region in Xq22.3, including the HERV-W locus, we identified three polymorphisms: rs6622139 (T/C), rs6622140 (G/A) and rs1290413 (G/A). After genotyping 3127 individuals (1669 MSers and 1458 controls) from two different Spanish cohorts, we found that in women rs6622139 T/C was associated with MS susceptibility: [chi2; p = 0.004; OR (95% CI) = 0.50 (0.31-0.81)] and severity, since CC women presented lower MSSS scores than CT (U-Mann-Whitney; p = 0.039) or TT patients (U-Mann-Whitney; p = 0.031). Concordantly with the susceptibility conferred in women, rs6622139*T was associated with higher MSRV expression (U-Mann-Whitney; p = 0.003). CONCLUSIONS: Our present work supports the hypothesis of a direct involvement of HERV-W/MSRV in MS pathogenesis, identifying a genetic marker on chromosome X that could be one of the causes underlying the gender differences in MS. Gavin Giovannoni at 12:00 life well LivedThursday, January 16, 2014 1:43:00 pm I read the Black Swan after your last post on it and talking with medical researchers at a conference at the National Academy of Medicine (where I told attendees we need blogs far more blogs like this). It's a great book which should be read to remind us how much of the very important unknown we don't even recognize as unknown. In any event, it shaped my thinking and writing on MS for months after reading it. As I tried to write about it, I still kept coming back to my same problem with a lot of MS research. Why do we treat MS as one disease? In the book, Talebin gives the example of the ice cube melting. If it is shaped like a mini swan, we can predict what it will look like in an hour at a sauna. However, if the first time we saw it was after the hour, we would have a hard time saying whether it was just a cube or an intricate swan. For MS at this point in our research, wouldn't it be more like coming into the sauna and seeing a bunch of puddles or a single wet sponge, and then trying to say with certainty what caused the wetness? MS presents differently, progresses differently, and responds to different drugs. Yet, we treat as if all RRMS are the same illness. Does the lack of differentiation cause some effective DMTs to have non statistically significant results? This was one of my take aways from the book. Thanks for recommending it.