Scientists involved in a new study are convinced that the Epstein-Barr virus (EBV), which has previously been linked to lupus, applies to 100% of all lupus cases. The findings could trigger new treatment for lupus and speed up a vaccine for EBV, which has also been linked to other autoimmune diseases, notes MedicalBrief.
The common childhood virus appears to be the trigger for the autoimmune disease, according to the US scientists, whose study suggests that 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, reports The Guardian.
“We think it applies to 100% of lupus cases,” said Professor 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 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, also an 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, and 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 one in 10 000 B cells hosted EBV, compared with about one in 400 cells for the lupus group – a 25-fold difference. EBV was also more likely to be found in auto-reactive 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
Professor 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.
NBC News reports that if confirmed, the findings would not only add impetus to clinical trials for an EBV vaccine, which are already under way, but add to the work of several teams exploring repurposing cancer treatments designed to wipe out B cells for severe cases of lupus.
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 Centre at Columbia University, who wasn’t involved in the new research.
“From our perspective, it’s the key, missing mechanistic link,” Robinson said.
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 non-profit organization is a private funder of lupus research and contributed grant funding to Robinson’s study.
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 reprogrammes 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.
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.
The findings are published in the journal Science Translational Medicine.
Study details
Epstein-Barr virus reprograms autoreactive B cells as antigen-presenting cells in systemic lupus erythematosus
Shady Younis, Salvinaz Moutusy, Sajede Rasouli et al.
Published in Science Translational Medicine on 12 November 2025
Abstract
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterised by antinuclear antibodies (ANAs). Epstein-Barr virus (EBV) infection has been epidemiologically associated with SLE, yet its role in pathogenesis remains incompletely defined. Here, we developed an EBV-specific single-cell RNA-sequencing platform and used it to demonstrate that EBV infection reprograms autoreactive antinuclear antigen B cells to drive autoimmunity in SLE. We demonstrated that, in SLE, EBV+ B cells are predominantly CD27+CD21low memory B cells that are present at increased frequencies and express ZEB2, TBX21 (T-bet), and antigen-presenting cell transcriptional pathways. Integrative analysis of chromatin immunoprecipitation sequencing (ChIP-seq), assay for transposase-accessible chromatin sequencing (ATAC-seq), and RNA polymerase II occupancy data revealed EBV nuclear antigen 2 (EBNA2) binding at the transcriptional start sites and regulatory regions of CD27, ZEB2, and TBX21, as well as the antigen-presenting cell genes demonstrated to be up-regulated in SLE EBV+ B cells. We expressed recombinant antibodies from SLE EBV+ B cells and demonstrated that they bind prototypical SLE nuclear autoantigens, whereas those from healthy individuals do not. We further found that SLE EBV+ B cells can serve as antigen-presenting cells to drive activation of T peripheral helper cells with concomitant activation of related EBV− antinuclear double-negative 2 B cells and plasmablasts. Our results provide a mechanistic basis for EBV being a driver of SLE through infecting and reprogramming nuclear antigen-reactive B cells to become activated antigen-presenting cells with the potential to promote systemic disease–driving autoimmune responses.
NBC News – All lupus cases may be linked to a common virus, study finds
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