Are missing the common viral link to MS disease activity? #MSBlog #MSResearch
"The study below raises interesting issue in relation to infection and MS. You should be aware by now that infections, both viral and bacterial, are a potent trigger of relapses. A third or relapses are preceded by a symptomatic infections. We always assume that these infections need to be symptomatic, but why? A large number of viruses remain latent in our bodies and periodically reactivate, this is typical for members of the herpes family of viruses, in particular Epstein-Barr (EBV), cytomegalovirus (CMV) and human-herpesvirus 6 (HHV-6). Most of the time when these viruses reactivate they don't cause symptoms. However, when they do reactivate they boost the immune systems responses, either the amount of antibody that binds to viral proteins or the T-cell responses to the virus. The study below suggests that this may be happening with HHV-6; before relapses the titre of antibody to the virus increases indicating that it HHV-6 had reactivated prior to the relapse, stimulating the immune system to produce higher levels of antibodies. This was quite a large study and hence not all MSers would necessarily have contributed to the positive results. What I am trying to say is that it may not necessarily be HHV-6 triggering relapses in all subjects; in some subjects it could could possibly be EBV, and in others influenzae. An interesting aspect of this study is that they linked the rising titre or level of antibody to DMT response; whether the link with DMT response is causal or simply an association needs to be looked at in future studies."
"This study may have therapeutic implications, i.e. suppressing viral reactivation may works as DMT, hence the search for better and safer antiviral therapies. The earlier trials of the anti-herpes drug acyclovir were negative in MS, but this drug, and its derivative valacyclovir, are not really effective against most of the herpes viruses including HHV-6. Therefore, I think it is time we go back to the funding agencies with our proposal to test a drug that targets EBV and other herpes viruses in MS."
|Model of what an HHV-6 viral particle looks like!|
Ortega-Madueño et al. Anti-Human Herpesvirus 6A/B IgG Correlates with Relapses and Progression in Multiple Sclerosis.PLoS One. 2014 Aug 11;9(8):e104836
OBJECTIVE: To analyze the titres of the IgG and IgM antibodies against human herpesvirus 6A/B (HHV-6A/B) in MSers treated with different disease modified therapies (DMTs) along two-years of follow-up.
METHODS: We collected 2163 serum samples from 596 MSers; for 301 MSers a 2-years follow-up was performed. Serum samples of 337 healthy controls were also analyzed. Anti-HHV-6A/B IgG and IgM were analyzed by ELISA (Panbio).
RESULTS: We found that 129/187 (69.0%) MSers with a decrease of the anti-HHV-6A/B IgG titres after 2-years with DMTs were free of relapses and progression vs. 46/113 (40.7%) of MSers with an increase of the anti-HHV-6A/B IgG titres (p = 0.0000015); the higher significance was found for natalizumab. Furthermore, we found that anti-HHV-6A/B IgG titres reached their highest value two weeks before the relapse (p = 0.0142), while the anti-HHV-6A/B IgM titres reached their highest value one month before the relapse (p = 0.0344).
CONCLUSION: The measurement of the anti-HHV-6A/B IgG titres could be a good biomarker of clinical response to the different DMTs. The increase of the anti-HHV-6A/B IgG and IgM titres predicts the upcoming clinical relapses. However, further longitudinal studies are needed to validate these results.