If you ask people with multiple sclerosis (multiple sclerosis or multiple sclerosis), they will probably tell you that their illness started with very few changes that they almost did not notice: trembling steps, weakening limbs, and blurred vision.
But MRI scans of their brains (which are full of white lesions) tell a different story. These lesions are inflammatory traces that go back several years. Each point represents a dead zone full of the destroyed remnants of thousands and sometimes millions of neurons.
Like city blocks that darken when a power outage occurs, these cells shut down one after another after an attack by the immune system destroys the myelin sheath, which helps them send and receive electrical signals. But it is not clear what triggers the immune system to launch such an attack.
Researchers have now found strong evidence that this agent is a type of infection, specifically the Epstein-Barr virus, which is best known for causing mononucleosis.
In a large group of soldiers who had been followed for several years, Epstein-Barr infections more than increased the risk of multiple sclerosis by more than 32 times, a group of scientists led by Harvard University’s Neuroepidemiology Research Group reported in the journal Science. “The study’s lead author, Harvard University Caitlin Bjornwick, said:
Our data strongly suggest that Epstein-Barr virus is the leading cause of multiple sclerosis. This was a dramatic increase in risk that is difficult to explain in other ways.
More than a decade ago, Alberto Escherio, a biologist at Harvard’s Bjornwick, speculated that the answer to the question of what triggers inflammation could be found at the Walter Reed Military Research Institute (WRAIR) in the United States. Since 1985, scientists there have taken blood samples from US military members every few years, screening and storing them (at minus 30 degrees Celsius). With more than 62 million samples from more than 10 active and reserve members, this serum tank is the largest collection of its kind in the world.
For biomedical researchers, this serum reservoir is their Hubble Telescope. This repository allows them to not only examine people’s bodies in depth, but also to study the pre-disease period.
This is especially important in the case of inflammation, as it is often diagnosed in the third and fourth decades of life. To check for these people before they become ill, you must start sampling as a teenager, when most people enroll in the military.
Inflammation of the brain is one of the most common side effects of viral infections. Millions of people with long cavities are witnessing this.
In the early 2000s, Ashrio and others found clues that suggested that the trigger for inflammation might be Epstein-Barr virus, or EBV. Epstein-Barr virus is a common member of the herpesvirus family. The virus is found in patients with inflammatory bowel disease in areas where their myelin is damaged. Also, people with high levels of anti-EBV antibodies were more likely to be diagnosed with inflammation.
Ashrio, one of the authors of a new article, turned to a nature experiment that took place in the serum reservoir to confirm that one factor causes another.
Physicians who treat and study patients with multiple sclerosis agree that this study convincingly demonstrates that EBV is both essential and pre-existing for the diagnosis of inflammatory bowel disease. “This is a very interesting article that expands our understanding of the role of EBV in causing inflammation,” John Korboy, a neuroscientist and director of the Rocky Mountain Inflammation Center at the University of Colorado, told the STAT news website via email; But he said it was too early to say whether the virus alone was enough to cause inflammation. For example, the study does not explain why only a small number of people infected with EBV develop inflammation. “Many unanswered questions remain about pathogenicity,” Corboy wrote.
Michael Wilson, a neuroscientist at the University of California, San Francisco who specializes in unknown neurological inflammatory disorders, said the study shows a chronological sequence of events that leads to the diagnosis of inflammation.
The Harvard team was not just looking for signs of the EBV virus itself or antibodies against it. They were also looking for markers called light chain neurofilaments (NfL). When neurons are attacked, they release these fibrous pieces, some of which leak into the cerebrospinal fluid and eventually enter the bloodstream. Studies have shown that a few years before the onset of inflammation, an increase in the level of light chain neurofilaments occurs.
New research has shown that this marker of nerve damage does not increase until after infection. This finding contradicts the argument that inflammation affects the immune system, making it more vulnerable to EBV infection.
The new study does not explain how EBV may start multiple sclerosis. Other research groups have speculated that the virus may carry myelin-like proteins. This phenomenon is called molecular imitation or pretending and can trigger an autoimmune reaction.
Others have suggested that because EBV often stays in B cells for a long time, latent infection may alter these immune cells and make them pathogenic. “The theory has been around for a long time that inflammation is a multifactorial disease,” Wilson said.
Studies have shown that some genes can also increase the risk of developing it. Also, not getting enough vitamin D can cause this. These factors, combined with environmental exposure such as a viral infection, may be sufficient to initiate disease. Wilson added:
EBV is probably not the whole story, but this study helps to show that EBV is clearly a part of it. The exciting thing is that this part of the story can be changed.
The world we inherited from our parents is fixed. But EBV is a virus, so our immune system can be trained to prevent infection.
There is currently no vaccine against EBV. Not much effort has been made to develop a vaccine against the virus. The reason for this is technical issues and lack of investment because the virus is not initially life threatening.
But such studies show that we need to do more to develop a vaccine against EBV. In addition to inflammation, the virus has been linked to a variety of cancers and other autoimmune diseases, such as lupus. Wilson said:
Understanding the exact mechanism of how EBV triggers inflammation is more of an academic question. For a general vaccination program, we only need to show that the vaccine reduces the incidence of tuberculosis, even if we do not know the exact mechanism.
There are examples of such movements. In 2006, regulators approved a vaccine to prevent the spread of four strains of human papillomavirus, or HPV. The virus increases the risk of cervical cancer.
While Americans delayed receiving the HPV vaccine, vaccine acceptance in the UK was very high. A recent analysis showed that these vaccines almost eliminated cervical cancer in young women in this country. Bjornwick said:
If EBV causes inflammation, it can shift the focus of research to find a cure for inflammation and also motivate the development of a vaccine. This study may also change research priorities for other neurological diseases.
Scientists have also found evidence that Alzheimer’s disease may also be caused by viral infections, including herpesviruses. However, these studies have been ridiculed many times, and this has led to no budget for them and the hypotheses of these scientists have not been examined. “Our findings in the field of inflammatory bowel disease are very specific, but we expect them to be of interest in re-examining the infectious causes of other diseases,” Bjornwick said.