New research may provide clues to an enduring mystery about multiple sclerosis and the common germ thought to be its leading cause, the Epstein-Barr virus. Scientists in Sweden have found that some patients with multiple sclerosis produce antibodies against the virus that seem to also mistakenly target a protein found in the brain and spinal cord. The findings provide more evidence that the Epstein-Barr virus can cause multiple sclerosis, the study authors say, and could help explain why some patients experience more severe illness than others.
Multiple sclerosis, or MS, is caused by an overzealous immune system that attacks our nervous system’s myelin sheath—a protective coating around nerve cells. The loss of myelin not only makes nerve cells more vulnerable but also hampers their ability to communicate with each other. As a result, people with MS can experience a variety of neurological symptoms, including numbness, muscle weakness, pain, and difficulty walking. MS patients tend to experience bouts of illness that fade and reoccur at first, but they will often eventually develop worsening symptoms that don’t go away.
It’s long been suspected that viral infections are a key trigger for MS, with the leading suspect being the Epstein-Barr virus, or EBV. Last year, a large study provided the strongest evidence yet for this connection. It found that military personnel newly infected with EBV were noticeably more likely to develop MS than those who avoided infection.
At the same time, there remain many questions about this link. Most everyone will contract EBV at some point in their lives. Some people might get momentarily sick from the infection (EBV is a major cause of mono). But only a few—less than 1% of the population—will later develop MS. So something else must be helping fuel the process that starts with EBV infection and ends with multiple sclerosis.
One leading theory for how EBV can cause MS is tied to a concept called molecular mimicry. Put simply, it’s the idea that EBV or a piece of it (also known as an antigen) can closely resemble proteins or other molecules naturally occurring in the body. When our immune system tries to mount a defense against infection, it might sometimes learn to target both EBV and these friendly bystanders, leading to MS.
In a study published Wednesday in Science Advances, researchers at the Karolinska Institute in Sweden and elsewhere present evidence that this chain of events is happening in at least some patients with EBV.
The authors studied blood samples collected from more than 700 MS patients and compared them to samples from similarly matched controls. Based on previous research, they decided to focus on one particular protein found throughout the brain and body that could be mistaken for EBV, called CRYAB. Among other functions, CRYAB is thought to help keep certain proteins from forming into potentially harmful clumps.
They found that MS patients were more likely to produce autoantibodies against CRYAB. They also showed that these antibodies could cross-react to a specific antigen of the virus—one that their previous research has linked to the development of MS. Lastly, they found some evidence that this cross-reaction can also happen in T cells, another key part of the immune system.
“We have identified that the immune response to EBV—which should normally control infection—instead has the ability to target human proteins, which could be involved in multiple sclerosis development or progression,” study author Olivia Thomas, a researcher at the Karolinska Institute, told Gizmodo. “This is further evidence that EBV infection may cause the immune system to mistakenly attack tissues in the body, and we found that these antibody responses, namely to alpha crystallin B and EBNA1 from EBV, are more frequent in persons with MS.”
The findings, while important, aren’t likely to explain every case of MS. For instance, only about 23% of MS patients seemed to have these cross-reactive antibodies to CRYAB. But it’s possible that there are several other native molecules that can be mistaken for EBV by the immune system and can thus spark MS, the authors say. This might also explain why no two MS patients experience the illness in the same way.
The researchers next plan to look more closely at how miscalibrated T cells can contribute to MS. Elsewhere, drug companies are starting to conduct human trials of treatments meant to eradicate chronic EBV, in hopes of stopping or slowing down the progression of MS, some of which have already shown early promise.
