Scientists Discover How a Common Virus Triggers Lupus—And It Could Change Treatment Forever

Stanford Medicine scientists have identified how the Epstein-Barr virus (EBV) serves as a crucial trigger in lupus development, revealing why this devastating autoimmune disease occurs. The virus, which quietly lives in 19 out of 20 Americans, hijacks immune cells and transforms them into inflammatory masterminds that orchestrate attacks on the body's own tissues. While EBV appears to be a necessary factor in lupus development, other genetic or environmental factors likely also play a role, as the vast majority of EBV-infected people never develop the disease.

How Does the Epstein-Barr Virus Contribute to Lupus?

The research reveals a complex mechanism where EBV-infected immune cells called B cells become inflammatory leaders that recruit armies of other immune cells to attack healthy tissue. In lupus patients, the number of EBV-infected B cells jumps dramatically to 1 in 400—a 25-fold increase compared to healthy people who have fewer than 1 in 10,000 infected cells.

"This is the single most impactful finding to emerge from my lab in my entire career," said Dr. William Robinson, professor of immunology and rheumatology at Stanford Medicine and the study's senior author. "We think it applies to 100% of lupus cases." Dr. Robinson's statement refers to the applicability of this EBV-mediated mechanism in lupus pathogenesis, though EBV infection alone is not sufficient to cause the disease.

What Makes This Discovery Groundbreaking?

The breakthrough came from developing an extremely high-precision sequencing system that can identify which B cells harbor the dormant virus—something previously impossible with existing methods. The researchers discovered that latent EBV occasionally produces a viral protein called EBNA2, which acts like a molecular switch, activating inflammatory genes in the infected B cell.

This process creates a cascade effect where infected B cells become "professional antigen-presenting cells" that stimulate helper T cells, which then enlist more immune cells to attack the body's cell nuclei—the hallmark of lupus damage. The net effect transforms a tiny number of infected cells into powerful orchestrators of widespread autoimmune attacks.

Could This Lead to Revolutionary Lupus Treatments?

While current lupus treatments focus on suppressing the immune system, this discovery opens doors to more targeted approaches. Scientists are already exploring revolutionary treatments that could reset malfunctioning immune systems rather than just dampening them.

Promising new approaches being tested include:

• CAR-T Therapy: Originally developed for cancer, this treatment reprograms a patient's T cells to destroy problematic B cells, potentially rebooting the entire immune system to produce healthy cells
• Regulatory T Cell Engineering: Scientists are enhancing "peacekeeper" immune cells that naturally calm autoimmune reactions and prevent attacks on healthy tissue
• Precision B Cell Targeting: Researchers are developing treatments that only eliminate "rogue" immune cells while preserving healthy ones that fight infections

Early results from these experimental treatments have been remarkable. One lupus patient treated with CAR-T therapy has remained in complete remission—without any other medication—since March 2021. A recent study of 10 patients treated with a T cell engager drug showed that six achieved drug-free remission.

"We're entering a new era," said Dr. Maximilian Konig, a rheumatologist at Johns Hopkins University studying these new treatments. "They offer the chance to control disease in a way we've never seen before."

The EBV-lupus connection has been suspected for years since essentially everyone with lupus is EBV-infected, but the mechanism remained mysterious until now. The virus typically infects people in childhood through sharing utensils or drinks, or during teenage years through kissing—earning it the nickname "the kissing disease" when it causes mononucleosis. "Practically the only way to not get EBV is to live in a bubble," Robinson noted.

Several hundred thousand Americans and about 5 million people worldwide have lupus, with women making up 90% of patients for unknown reasons. While current treatments help most patients live reasonably normal lives, about 5% face life-threatening complications. This groundbreaking research could finally provide the precise, curative treatments that lupus patients have been waiting for.