Now a virus that isn’t associated with MS

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Cytomegalovirus (CMV) is related to the herpes virus that causes cold sores and chick pox. It gets its name from making cells swell/go big. Like EBV Once you have the virus, it stays in your body for the rest of your life. Your immune system usually controls the virus and most people do not realise they have it. But CMV can cause serious health problems in some babies who get the virus before birth, and in people who have a weakened immune system.

Symptoms of cytomegalovirus (CMV)

CMV does not usually cause symptoms.

Some people get flu-like symptoms the first time they get CMV, including:

  • a high temperature
  • aching muscles
  • tiredness
  • skin rash
  • feeling sick
  • sore throat
  • swollen glands

Grut V, Biström M, Salzer J, Stridh P, Jons D, Gustafsson R, Fogdell-Hahn A, Huang J, Brenner N, Butt J, Bender N, Lindam A, Alonso-Magdalena L, Gunnarsson M, Vrethem M, Bergström T, Andersen O, Kockum I, Waterboer T, Olsson T, Sundström P. Cytomegalovirus seropositivity is associated with reduced risk of multiple sclerosis – a presymptomatic case-control study. Eur J Neurol. 2021 Jun 9. doi: 10.1111/ene.14961.

Background: Epstein-Barr virus (EBV) and Human herpesvirus 6A (HHV-6A) are associated with increased risk of multiple sclerosis (MS). Conversely, infection with Cytomegalovirus (CMV) has been suggested to reduce the risk of MS but supporting data from presymptomatic studies are lacking. Here, we sought to increase the understanding of CMV in MS aetiology.

Methods: We performed a case-control study with presymptomatically collected blood samples identified through cross-linkage of MS registries and Swedish biobanks. Serological antibody response against CMV, EBV and HHV-6A was determined using a bead-based multiplex assay. Odds ratio (OR) with 95 % confidence intervals (CI) for CMV seropositivity as risk factor for MS was calculated by conditional logistic regression and adjusted for EBV and HHV-6A seropositivity. Potential interactions on the additive scale were analysed by calculating attributable proportion due to interaction (AP).

Results: Serum samples from 670 pairs of matched cases and controls were included. CMV seropositivity was associated with a reduced risk for MS (OR = 0.70, 95% CI 0.56-0.88, p = 0.003). Statistical interactions on the additive scale were observed between seronegativity for CMV and seropositivity against HHV-6A (AP 0.34, 95% CI 0.06-0.61) and EBV antigen EBNA-1 (amino acid 385-420) at age 20-39 years (AP 0.37, 95% CI 0.09-0.65).

Conclusions: CMV seropositivity is associated with a decreased (30%) risk for MS. The protective role for CMV infection in MS aetiology is further supported by the interactions between CMV seronegativity and EBV and HHV-6A seropositivity

And whilst we are on viruses

Wu J, Engdahl E, Gustafsson R, Fogdell-Hahn A, Waterboer T, Hillert J, Olsson T, Alfredsson L, Hedström AK. High antibody levels against human herpesvirus-6A interact with lifestyle factors in multiple sclerosis development. Mult Scler. 2021 Jun 14:13524585211022011. doi: 10.1177/13524585211022011.

Background: Infection with human herpesvirus 6A (HHV-6A) has been suggested to increase multiple sclerosis (MS) risk. However, potential interactions between HHV-6A and environmental/lifestyle risk factors for MS have not previously been studied.

Methods: We used two Swedish population-based case-control studies comprising 5993 cases and 5995 controls. Using logistic regression models, subjects with different HHV-6A antibody levels, environmental exposures, and lifestyle habits were compared regarding MS risk, by calculating odds ratios (ORs) with 95% confidence intervals (CIs). Potential interactions between high HHV-6A antibody levels and common environmental exposures and lifestyle factors were evaluated on the additive scale.

Results: High HHV-6A antibody levels were associated with increased risk of developing MS (OR = 1.5, 95% CI = 1.4-1.6). Regarding MS risk, significant interactions were observed between high HHV-6A antibody levels and both smoking (attributable proportion (AP) = 0.2, 95% CI = 0.1-0.3), low ultraviolet radiation (UVR) exposure (AP = 0.3, 95% CI = 0.1-0.4), and low vitamin D levels (AP = 0.3, 95% CI = 0.0-0.6).

Conclusion: High HHV-6A antibody levels are associated with increased MS risk and act synergistically with common environmental/lifestyle risk factors for MS. Further research is needed to investigate potential mechanisms underlying the interactions presented in this study.

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MouseDoctor

10 comments

  • Is it me or does it feel like MS research is splitting hairs? Who cares about your 0 impact studies. If you have a hypothesis, test it. Not sure what this study aims to achieve, should we infect MSers with CMV? And yeah, just as an interesting tidbit, Moderna is testing a CMV vaccine.

    • It’s much harder to fix something if you don’t understand the causes. Research with no immediate benefit is still useful and absolutely necessary in the long run.

  • I am a patient of Prof G and suffered from a nasty primary CMV infection (night sweats for a month, steep weight loss…) about 5ys after starting Tysabri…

  • In the raft of tests done when diagnosed the one which came back positive was CMV which at the time I had never heard of. A prime example of correlation not being causation then. But why were they testing for this when they already thought it was likely MS? Its absence?

  • Cmv and ebv use some of the same pathways to infect an individual therefore infection with cmv might be able to reduce the number of people getting infected with ebv through the antibody production against certain cmv spike proteins that ebv also uses.

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