A common childhood virus may be a trigger for the autoimmune disease lupus, according to groundbreaking research.
The study suggests that the Epstein-Barr virus (EBV), which is harmless to most people, can cause immune cells to go “out of control” and mistakenly attack the body's own tissues. The team behind the work said uncovering the cause of lupus could revolutionize treatment.
“We think this applies to 100% of lupus cases,” said Professor William Robinson, professor of immunology and rheumatology at Stanford University and senior author of the study. “I think this really sets the stage for a new generation of treatments that could fundamentally treat and thereby benefit patients with lupus.”
Lupus, which affects around 69,000 people in the UK, is a chronic autoimmune disease in which the immune system produces antibodies that attack the body's own tissues. The causes are not fully understood and there is no known treatment for the condition, which can cause joint and muscle pain, severe fatigue and skin rashes.
Epidemiological studies have previously hinted at a link between EBV and lupus. This idea has gained traction following a recent discovery showing Link between EBV and multiple sclerosisanother autoimmune disease. The latest work helps reveal at the cellular level how EBV causes lupus by sending the immune system into a tailspin.
“This study solves a decades-old mystery,” said Shady Younis, an immunologist at Stanford and first author of the paper.
EBV is usually a mild illness that causes a sore throat, fever, and tonsillitis. By adulthood, about 19 out of 20 people become infected and – because the virus deposits its genetic material in DNA – carry the dormant virus in their cells.
“The reason it's so surprising is because it's a common virus that most of us get from a sibling at the kitchen table as we get older, or if not, when we kiss someone else as a teenager,” Robinson said. “Pretty much the only way to avoid getting EBV is to live in a bubble.”
Among the cell types in which EBV resides are B cells, which are part of the immune system. These cells specialize in binding to proteins on the surface of viruses known as antigens. About 20% of B cells also have the potential to bind to parts of the body's own cells, but in healthy people these “autoreactive” B cells remain largely inactive.
Scientists used high-precision genetic sequencing for the first time to identify differences in the number and type of infected B cells in 11 lupus patients compared with 10 healthy controls.
In the control group, fewer than 1 in 10,000 B cells contained EBV, compared with about 1 in 400 cells in the lupus group—a 25-fold difference. EBV was also more frequently detected in autoreactive B cells.
The presence of the dormant virus appeared to put these cells into a hyperactive state in which they not only targeted antigens within the body but also recruited other immune cells, including killer T cells, to attack.
“We think this is a critical finding: EBV…then activates these B cells to trigger the autoimmune response that mediates lupus,” Robinson said.
In addition to EBV, there are other well-known risk factors that influence a person's susceptibility. For example, lupus disproportionately affects women, which may be because hormones like estrogen increase B-cell activity, Robinson said. People of African, Caribbean or Asian descent are also at higher risk.
Professor Guy Gorokhov, professor of medicine at the Sorbonne University, said the work was “impressive”.
“This is not the last paper on lupus, but they have done a lot and developed an interesting concept,” he said.
If confirmed, these findings will provide impetus to clinical trials of an EBV vaccine that are already underway. There are also several teams exploring the possibility of repurposing cancer treatments designed to kill B cells in severe cases of lupus.
The results were published in the journal Scientific translational medicine.
