Epstein-Barr virus may drive all Lupus cases, finds study

November 17, 2025: A study from Stanford Medicine has provided the strongest evidence yet that the Epstein-Barr virus (EBV) may be the root cause of systemic lupus erythematosus (SLE), a chronic autoimmune disease that affects millions worldwide.

The research reveals how EBV can reprogram immune cells to trigger lupus in genetically susceptible individuals.

EBV, a member of the herpesvirus family, infects approximately 95% of adults globally and is best known for causing infectious mononucleosis. Once contracted, the virus remains dormant in the body, typically within B cells—the same immune cells that go awry in lupus. The Stanford team, led by Dr. William Robinson, found that EBV can hijack these B cells, turning them into rogue agents that orchestrate an autoimmune attack on the body’s own tissues.

Using RNA sequencing and cellular analysis, the researchers discovered that EBV-infected B cells in lupus patients express genes such as ZEB2 and TBX21, which activate helper T cells. These T cells then stimulate other B cells—even uninfected ones—to produce antinuclear antibodies, a hallmark of lupus. This chain reaction creates a self-perpetuating cycle of immune dysfunction that underlies the disease’s systemic inflammation and organ damage.

Crucially, the study found that EBV-infected B cells are 25 times more prevalent in lupus patients than in healthy individuals. The virus appears to produce a protein called EBNA2, which binds to human DNA and enhances the expression of genes involved in autoimmunity. This mechanism offers a direct molecular link between EBV infection and lupus onset.

Dr. Robinson called the discovery “the single most impactful finding to emerge from my lab,” suggesting that EBV may be responsible for 100% of lupus cases. While not everyone infected with EBV develops lupus, the researchers believe that genetic and environmental factors determine who is most at risk. “It’s EBV infection in the context of the genetic and environmental milieu that predisposes one to lupus,” Robinson explained.

The implications of this discovery are profound. For decades, lupus has been treated with broad immunosuppressive drugs that manage symptoms but do not address the underlying cause. Now, scientists are exploring antiviral therapies and CAR T-cell treatments that specifically target EBV-infected B cells. Early trials of CAR T-cell therapy have shown promising results, with some lupus patients achieving long-term remission without medication—possibly by eliminating the EBV-infected cells driving the disease.

Experts caution that while the evidence is compelling, more research is needed to confirm EBV’s role in all lupus cases. “Although the evidence is intriguing, more studies are required to demonstrate that the link applies universally,” said Hoang Nguyen of the Lupus Research Alliance.

Nonetheless, the findings mark a turning point in autoimmune research. By identifying a common viral trigger, scientists now have a clear target for prevention and treatment strategies. Calls are growing for the development of an EBV vaccine, which could potentially prevent not only lupus but also other autoimmune diseases linked to the virus, such as multiple sclerosis and rheumatoid arthritis.

As research continues, the Stanford study offers new hope to the millions living with lupus—a disease that may no longer be as mysterious as once thought.