A common childhood virus appears to be the trigger for the autoimmune disease lupus, according to groundbreaking research.
The study suggests that Epstein-Barr virus (EBV), which for most people is harmless, can cause immune cells to “go rogue” and mistakenly attack the body’s own tissues. The team behind the work said that uncovering the cause of lupus could revolutionise treatments.
“We think it applies to 100% of lupus cases,” said Prof William Robinson, a professor of immunology and rheumatology at Stanford University and the study’s senior author. “I think it really sets the stage for a new generation of therapies that could fundamentally treat and thereby provide benefit to lupus patients.”
Lupus, which affects about 69,000 people in the UK, is a chronic autoimmune condition in which the immune system creates antibodies that attack the body’s own tissues. The causes have not been well understood and there is no known cure for the condition, which can cause joint and muscle pain, extreme tiredness and skin rashes.
Epidemiological surveys have previously hinted at a link between EBV and lupus, an idea that has gained traction after a recent breakthrough proving the link between EBV and multiple sclerosis, another autoimmune disorder. The latest work helps uncover, at a cellular level, how EBV appears to cause lupus by sending the immune system into a tailspin.
“This study resolves a decades-old mystery,” said Shady Younis, an immunologist at Stanford and first author of the paper.
EBV is typically a mild illness which causes a sore throat, fever and tonsillitis. By adulthood, about 19 out of 20 people become infected and – since the virus deposits its genetic material into DNA – carry the dormant virus in their cells.
“The reason why this is so surprising is because this is a common virus that most of us get from our brother or sister at the kitchen table when we’re growing up, or if we haven’t, then when we kiss somebody else as a teenager,” said Robinson. “Practically the only way to not get EBV is to live in a bubble.”
Among the cell types in which EBV takes up permanent residence are B cells, part of the immune system. These cells are specialised at 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 individuals these “autoreactive” B cells remain largely inactive.
The scientists first used high-precision genetic sequencing to uncover differences in the number and type of B cells that are infected in 11 lupus patients compared with 10 healthy controls.
In the control group, fewer than 1 in 10,000 B cells hosted EBV, compared with about 1 in 400 cells for the lupus group – a 25-fold difference. EBV was also more likely to be found in autoreactive B cells.
The presence of the dormant virus appeared to flip these cells into a hyperactive state in which they not only targeted antigens inside the body, but recruited other immune cells, including killer T-cells, to join the attack.
“We think this is the critical discovery: that EBV … then activates those B cells to drive the autoimmune response that mediates lupus,” said Robinson.
There are other well-known risk factors that feed into a person’s susceptibility, beyond EBV. For instance, lupus disproportionately affects women, which could be due to hormones such as oestrogen amplifying B-cell activity, Robinson said. People with an African, Caribbean or Asian background are also at a higher risk
Prof Guy Gorochov, a professor of medicine at the Sorbonne University said the work was “impressive”.
“It’s not the final paper about lupus, but they’ve done a lot and developed an interesting concept,” he said.
If confirmed, the findings would add impetus to clinical trials for an EBV vaccine, which are already under way. There are also several teams exploring repurposing cancer treatments designed to wipe out B cells for severe cases of lupus.
The findings are published in the journal Science Translational Medicine.
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