One of the most common viruses in the world could be the cause of lupus, an autoimmune disease with wide-ranging symptoms, according to a study published Wednesday.
Until now, lupus was somewhat mysterious: No single root cause of the disease had been found, and there is no designated treatment for it.
The research, published in the journal Science Translational Medicine, suggests that Epstein-Barr virus — which 95% of people acquire at some point in life — could cause lupus by driving the body to attack its own healthy cells.
It adds to mounting evidence that Epstein-Barr is associated with multiple long-term health issues, including other autoimmune conditions. As this evidence stacks up, scientists have accelerated calls for a vaccine that targets the virus.
“If we now better understand how this fastidious virus is responsible for autoimmune diseases, I think it’s time to figure out how to prevent it,” said Dr. Anca Askanase, clinical director of the Lupus Center at Columbia University, who wasn’t involved in the new research.
In lupus patients, an autoimmune attack can result in extreme fatigue, joint pain and skin rashes. In rare cases, the disease may lead to fatal or life-threatening issues such as kidney damage, or weaken the immune system so the body can’t fight off infections.
Scientists have long suspected a link between Epstein-Barr and lupus, but the exact connection had remained elusive. Dr. William Robinson, a co-author of the new study and chief of the division of immunology and rheumatology at Stanford University, said his new findings solve a major piece of that puzzle.
“From our perspective, it’s the key, missing mechanistic link,” Robinson said.
“We think it applies to all lupus cases,” he added. Hundreds of thousands of people in the U.S. are living with the disease.
But Hoang Nguyen, assistant vice president of research at the Lupus Research Alliance, said it’s too soon to know if the mechanism is behind every case.
“Although the evidence is intriguing and promising, more evidence is needed to demonstrate that the link to EBV applies to all lupus,” Nguyen said. The alliance is a private funder of lupus research and contributed grant funding to Robinson’s study.
An infection withe Epstein-Barr virus does not necessarily cause symptoms, especially among children, though the virus is also the most common cause of mononucleosis (often referred to as mono).
It's primarily transmitted by saliva from kissing or sharing drinks, food, utensils or toothbrushes. After someone is infected, the virus lingers permanently in the body, where it usually remains inactive — though not always.
The new study is not the first to tie Epstein-Barr to autoimmune issues. Past research has linked it to multiple sclerosis. Though not the sole trigger of MS, the virus may be part of a chain of events that leads to the disease.
Robinson said a pathway similar to the one described in his new study could also lead to other autoimmune diseases like rheumatoid arthritis and Crohn’s disease, but more research is needed to tease that out.
Of course, the vast majority of people who contract Epstein-Barr do not go on to get lupus, MS or any other autoimmune disease. Robinson said it’s possible that only certain strains of Epstein-Barr trigger autoimmune reactions.
To determine the causal link between Epstein-Barr and lupus, Robinson and his co-authors focused on B cells — white blood cells that help fight off infections.
Even in healthy individuals, Epstein-Barr lies dormant in a tiny portion of B cells. But those virus-containing B cells are far more prevalent in lupus patients, who have a 25 times higher share of them, according to the new research.
The study also highlights a type of protein called antinuclear antibodies, which bind to the nucleus of cells and are one of the hallmarks of lupus. The researchers found that Epstein-Barr infects and reprograms B cells to produce antinuclear antibodies that attack the body’s own tissue, thereby causing lupus.
Robinson said the findings go hand-in-hand with some other theories about what causes lupus. For instance, scientists suspect that a person’s genetics or hormones can predispose them to the disease, as well.
A study published last year in the journal Nature also found that people with lupus have too much of a particular T cell — another type of white blood cell — that’s associated with cell damage and too little of another T cell associated with repair. Robinson said the pathway described in his study could activate that T cell response.
The new research points to a few potential options for lupus treatment, according to Robinson, who is the co-founder of two drug development companies exploring treatments for autoimmune diseases.
Many of the current medications given to ease lupus symptoms, such as corticosteroids, broadly focus on reducing inflammation. Robinson said future therapeutics could specifically target B cells infected with Epstein-Barr.
But an Epstein-Barr vaccine — several of which are in clinical trials — could someday stop infections in the first place.
“Vaccination to protect people against ever being infected by EBV would be the ultimate, fundamental solution,” Robinson said.
