Epstein-Barr virus appears to be trigger of lupus disease, say scientists | Immunology

A common childhood virus appears to be the 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 make immune cells “rebellious” and mistakenly attack the body’s own tissues. The team behind the work said discovering the cause of lupus could revolutionize treatments.

“We think this applies to 100% of lupus cases,” said Professor William Robinson, professor of immunology and rheumatology at Stanford University and lead author of the study. “I think this really opens the door to a new generation of therapies that could fundamentally treat and thus provide benefit to lupus patients.”

Lupus, which affects around 69,000 people in the UK, is a chronic autoimmune disease in which the immune system creates antibodies that attack the body’s own tissues. The causes are not well understood and there is no known cure for the condition, which can cause joint and muscle pain, extreme fatigue and skin rashes.

Epidemiological investigations have already hinted at a link between EBV and lupus, an idea that gained traction after a recent breakthrough proving the link between EBV and multiple sclerosis, another autoimmune disease. The latest work helps uncover, at the cellular level, how EBV appears to cause 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. As adults, about 19 out of 20 people are infected and – since the virus deposits its genetic material in DNA – carry the dormant virus in their cells.

“The reason this is so surprising is because this is a common virus that most of us contracted from our sibling at the kitchen table when we were growing up, or if we didn’t, when we kissed someone else when we were teenagers,” Robinson said. “Practically, the only way to avoid contracting EBV is to live in a bubble. »

Among the cell types in which EBV becomes permanently established are B cells, which are part of the immune system. These cells are specialized in binding to proteins on the surface of viruses, called 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 discover differences in the number and type of infected B cells in 11 lupus patients compared to 10 healthy controls.

In the control group, fewer than 1 in 10,000 B cells harbored 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 appears to tip these cells into a hyperactive state in which they not only target antigens inside the body, but recruit other immune cells, including killer T cells, to join the attack.

“We think that’s the crucial finding: that EBV … then activates these B cells to drive the autoimmune response that mediates lupus,” Robinson said.

There are other well-known risk factors that contribute to a person’s susceptibility, beyond EBV. For example, lupus disproportionately affects women, which could be due to hormones such as estrogen that boost B-cell activity, Robinson said. People of African, Caribbean or Asian descent are also at higher risk

Professor Guy Gorochov, professor of medicine at 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 results would provide a boost to clinical trials already underway for an EBV vaccine. Several teams are also studying the reuse of anticancer treatments designed to eliminate B cells in severe cases of lupus.

The results are published in the journal Science Translational Medicine.