Shady Younis <\/p>\n
Infection by the Epstein-Barr virus (left) can cause B cells (in blue), the immune cells that produce antibodies, to activate other B cells that produce antibodies to proteins and DNA in cells throughout the body.
Shady Younis <\/p>\n
November 12, 2025<\/p>\n
Stanford Medicine scientists tie lupus to a virus nearly all of us carry <\/p>\n
By Bruce Goldman<\/p>\n
The Epstein-Barr virus can convert B cells it\u2019s infected into diabolical overlords that reprogram myriad other immune cells to attack our tissues, Stanford Medicine scientists have found.<\/p>\n
One of humanity\u2019s most ubiquitous infectious pathogens bears the blame for the chronic autoimmune condition called systemic lupus erythematosus or, colloquially, lupus, Stanford Medicine investigators and their colleagues have found.<\/p>\n
The Epstein-Barr virus (EBV), which resides silently inside the bodies of 19 out of 20 Americans, is directly responsible for commandeering what starts out as a minuscule number of immune cells to go rogue and persuade far more of their fellow immune cells to launch a widespread assault on the body\u2019s tissues, the scientists have shown.<\/p>\n
The findings were published Nov. 12 in Science Translational Medicine.<\/p>\n
\u201cThis is the single most impactful finding to emerge from my lab in my entire career,\u201d said William Robinson, MD, PhD, a professor of immunology and rheumatology and the study\u2019s senior author. \u201cWe think it applies to 100% of lupus cases.\u201d<\/p>\n
The study\u2019s lead author is Shady Younis, PhD, an instructor in immunology and rheumatology.<\/p>\n
Several hundred thousand Americans (by some estimates close to a million) and about 5 million worldwide have lupus, in which the immune system attacks the contents of cell nuclei. This results in damage to organs and tissues throughout the body \u2014 skin, joints, kidneys, heart, nerves and elsewhere \u2014 with symptoms varying widely among individuals. For unknown reasons, nine out of 10 lupus patients are women.<\/p>\n
William Robinson <\/p>\n
With appropriate diagnosis and medication, most lupus patients can live reasonably normal lives, but for about 5% of them the disorder can be life-threatening, said Robinson, who is the James W. Raitt, MD, Professor. Existing treatments slow down disease progression but don\u2019t cure it, he said.<\/p>\n
By the time we\u2019ve reached adulthood, the vast majority of us have been infected by EBV. Transmitted in saliva, EBV infection typically occurs in childhood, from sharing a spoon with or drinking from the same glass as a sibling or a friend, or maybe during our teen years, from exchanging a kiss. EBV can cause mononucleosis, \u201cthe kissing disease,\u201d which begins with a fever that subsides but lapses into a profound fatigue that can persist for months.<\/p>\n
\u201cPractically the only way to not get EBV is to live in a bubble,\u201d Robinson said. \u201cIf you\u2019ve lived a normal life,\u201d the odds are nearly 20 to 1 you\u2019ve got it.<\/p>\n
Once you\u2019ve been infected by EBV you can\u2019t get rid of it, Robinson said, even if you remain or become symptom-free. EBV belongs to a large family of viruses, including those responsible for chickenpox and herpes, that can deposit their genetic material into the nuclei of infected cells. There the virus slumbers in a latent form, hiding from the immune system\u2019s surveillance agents. This may last as long as the cell it\u2019s hiding in stays alive. Or, under certain conditions, the virus may reactivate and force the infected cell\u2019s replicative machinery to produce myriad copies of themselves that break out to infect other cells and other people.<\/p>\n
Among the cell types in which EBV takes up permanent residence are B cells, immune cells that do a couple of important things after they ingest bits of microbial pathogens. For one, they can produce antibodies: customized proteins that find and bind immune-system-arousing proteins or other molecules (immunologists call them \u201cantigens\u201d) on microbial pathogens that have infected an individual, or are trying to. For another, B cells are what immunologists call \u201cprofessional antigen-presenting cells\u201d: They can process antigens and display them on their surfaces in a way that encourages other immune cells to raise the intensity of their hunt for the pathogen in question. That\u2019s a substantial force multiplier for kick-starting an immune response.<\/p>\n
Our bodies harbor hundreds of billions of B cells, which over the course of numerous rounds of cell division develop an enormous diversity of antibodies. In the aggregate, these antibodies can bind an estimated 10 billion to 100 billion different antigenic shapes. This is why we\u2019re able to mount a successful immune response to so many different pathogens.<\/p>\n
Practically the only way to not get EBV is to live in a bubble.\u201d <\/p><\/blockquote>\n
Oddly, about 20% of the B cells in our bodies are autoreactive. They target antigens belonging to our own tissues \u2014 not by design, but due to the random way B-cell diversity comes about: through sloppy replication, apparently engineered by evolution to ensure diversification. Fortunately, these B cells are typically in a dopey state of inertia, and they pretty much leave our tissues alone.<\/p>\n
But at times, somnolent autoreactive B cells become activated, take aim at our own tissues and instigate one of the disorders collectively called autoimmunity. Some awakened autoreactive B cells crank out antibodies that bind to proteins and DNA inside the nuclei of our cells. Such activated \u201cantinuclear antibodies\u201d \u2014 the hallmark of lupus \u2014 trigger damage to tissues randomly distributed throughout the body, because virtually all our body\u2019s cells have nuclei.<\/p>\n
The vast majority of EBV-infected people (most of us, that is) have no idea they\u2019re still sheltering a virus and never get lupus. But essentially everyone with lupus is EBV-infected, studies have shown. An EBV-lupus connection has been long suspected but never nailed down until now.<\/p>\n
The antinuclear B cell gets ornery<\/h3>\n
Although latent EBV is ubiquitous in the sense that almost everybody carries it, it resides in only a tiny fraction of any given person\u2019s B cells. As a result, until the new study, it was virtually impossible for existing methods to identify infected B cells and distinguish them from uninfected ones. But Robinson and his colleagues developed an extremely high-precision sequencing system that enabled them to do this. They found that fewer than 1 in 10,000 of a typical EBV-infected but otherwise healthy individual\u2019s B cells are hosting a dormant EBV viral genome.<\/p>\n
Employing their new EBV-infected-B-cell-identifying technology along with bioinformatics and cell-culture experimentation, the researchers found out how such small numbers of infected cells can cause a powerful immune attack on one\u2019s own tissues. In lupus patients, the fraction of EBV-infected B cells rises to about 1 in 400 \u2014 a 25-fold difference.<\/p>\n
It\u2019s known that the latent EBV, despite its near-total inactivity, nonetheless occasionally nudges the B cell it\u2019s been snoozing in to produce a single viral protein, EBNA2. The researchers showed that this protein acts as a molecular switch \u2014 in geneticists\u2019 language a \u201ctranscription factor\u201d \u2014 activating a battery of genes in the B cell\u2019s genome that had previously been at rest. At least two of the human genes switched on by EBNA2 are recipes for proteins that are, themselves, transcription factors that turn on a variety of other pro-inflammatory human genes.<\/p>\n
The net effect of all these genetic fireworks is that the B cell becomes highly inflammatory: It dons its \u201cprofessional antigen-presenting cell\u201d uniform and starts stimulating other immune cells (called helper T cells) that happen to share a predilection for targeting cell-nuclear components. These helper T cells enlist multitudes of other antinuclear B cells as well as antinuclear killer T cells, vicious attack dogs of the immune system.<\/p>\n
When that militia bulks up, it doesn\u2019t matter whether any of the newly recruited antinuclear B cells are EBV-infected or not. (The vast majority of them aren\u2019t.) If there are enough of them, the result is a bout of lupus.<\/p>\n
What comes next?<\/h3>\n
Robinson said he suspects that this cascade of EBV-generated self-targeting B-cell activation might extend beyond lupus to other autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and Crohn\u2019s disease, where hints of EBV-initiated EBNA2 activity have been observed.<\/p>\n
The million-dollar question: If about 95% of us are walking around with latent EBV in our B cells, why do some of us, but not all of us, get autoimmunity? Robinson speculates that perhaps only certain EBV strains spur the transformation of infected B cells into antigen-presenting \u201cdriver\u201d cells that broadly activate huge numbers of antinuclear B cells.<\/p>\n
Many companies are working on an EBV vaccine, and clinical trials of such a vaccine are underway. But that vaccine would have to be given soon after birth, Robinson noted, as such vaccines are unable to rid an already-infected person of the virus.<\/p>\n
Stanford University\u2019s Office of Technology Licensing has filed a provisional patent application on intellectual property associated with the study\u2019s findings and technologies used to obtain them. Robinson, Younis and a third study co-author, Mahesh Pandit, PhD, a postdoctoral scholar in immunology and rheumatology, are named inventors on the application. They are co-founders and stockholders of a company, EBVio Inc., a company exploring an experimental lupus treatment, ultradeep B-cell depletion. This procedure involves total annihilation of all circulating B cells, which are replaced over the following few months by new, EBV-free B cells born continually in the bone marrow. Robinson is also a director of EBVio Inc. and a co-founder and shareholder of Flatiron Bio, LLC.<\/p>\n
Researchers from the U.S. Department of Veterans Affairs Medical Center, Cincinnati; the University of Massachusetts School of Medicine; the University of Oklahoma Health Sciences Center; and Rockefeller University contributed to the work.<\/p>\n
The study was funded by the National Institutes of Health (grants R01AR078268, R01AI173189-01, PATHO-PH2-SUB_17_23 and R01AI024717), the VA Palo Alto Health Care System, the Lupus Research Alliance and the Brennan Family.<\/p>\n
About Stanford Medicine<\/p>\n
Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit med.stanford.edu.<\/p>\n
<\/p>\n
Senior science writer<\/p>\n
Bruce Goldman<\/h2>\n
Bruce Goldman, MS, is a senior science writer in the Office of Communications. He covers immunology, infectious disease, transplantation, neurosciences, neurosurgery, bioengineering, molecular and cellular physiology, and biochemistry. A recovering philosophy major from the University of Wisconsin, he\u2019s done his best to cover his tracks by obtaining yet another bachelor\u2019s degree, this time in engineering physics from the University of Colorado, and attending finishing school, in cell biology, at Harvard University, where he received an award for his teaching of an undergraduate biology course. Articles he has written while at Stanford Medicine have won well over a dozen awards from the Association of American Medical Colleges and the Council for Advancement and Support of Education. He is a member of the National Association of Science Writers and the co-author of two books about the future: 2020 Visions: Long View of a Changing World (Portable Stanford) and Fast Forward (Harper). Once upon a time, he drove a car to Afghanistan. He can play guitar with his toes, but only while fast asleep and dreaming.<\/p>\n
goldmanb@stanford.edu Media Contact <\/p>\n
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- Bruce Goldman Tel 650-725-2106 goldmanb@stanford.edu <\/li>\n<\/ul>\n
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November 13, 2024 <\/p>\n
Key influenza-severity risk factor found hiding in plain sight on our antibodies <\/p>\n
Why do some people develop severe flu symptoms? A Stanford Medicine study points the finger at an unsung portion of the antibodies our immune systems generate to fend off invading pathogens.<\/p>\n<\/li>\n
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February 01, 2024 <\/p>\n
Stanford Medicine-led study shows why women are at greater risk of autoimmune disease <\/p>\n
Research throws light on the mystery of why women are much more prone to autoimmune disorders: A molecule made by one X chromosome in every female cell can generate antibodies to a woman's own tissues.<\/p>\n<\/li>\n
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January 24, 2022 <\/p>\n
Study identifies how Epstein-Barr virus triggers multiple sclerosis <\/p>\n
A new study found that part of the Epstein-Barr virus mimics a protein made in the brain and spinal cord, leading the immune system to mistakenly attack the body's nerve cells.<\/p>\n<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"
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