Stanford scientists find link between Epstein-Barr virus and lupus

The Epstein-Barr virus (EBV) has been linked to the development of systemic lupus erythematosus, according to research recently published in Science Translational Medicine.

A team of Stanford Medicine scientists, including first author Shady Younis, Ph.D., an instructor in immunology and rheumatology at the Stanford School of Medicine, and William Robinson, M.D., Ph.D., professor of medicine at the Stanford School of Medicine, found that in healthy patients, fewer than 1 in 10,000 EBV-infected B cells host a dormant EBV viral genome. In lupus patients, approximately 1 in 400 B cells harbors a dormant EBV viral genome.

“For decades, EBV has been linked to lupus and other autoimmune diseases, but the precise mechanisms were missing. In this study, we developed a method to directly detect the virus in patients’ B cells and uncovered how it reprograms them to drive autoimmune responses,” Younis said in a news release.

Almost all (19 in 20) Americans have been infected by EBV, which is spread through saliva. Transmission typically occurs in childhood, from things like sharing a spoon or a glass with someone who is infected. The virus is also responsible for “the kissing disease,” mononucleosis.

Once infected, EBV lives permanently in the body, even if someone is symptom-free. The virus survives by depositing its genetic material into the nuclei of infected cells, including B cells, which are immune cells that produce antibodies.

In some cases, cells that contain latent EBV producesEBNA2, a viral protein that activates B cells that become highly inflammatory and stimulates other immune cells called helper T cells, antinuclear B cells and antinuclear killer T cells. Activated antinuclear antibodies are the hallmark of lupus, and because nearly all cells in the body contain nuclei, the activated antibodies can cause widespread symptoms.

Autoimmune diseases, like lupus, are characterized by the body attacking itself. It currently affects approximately 1.5 million Americans. More than 200,000 Americans have systemic lupus erythematosus, which is the most common type of lupus. The most common symptom of lupus is fatigue, followed by muscle and joint pain, fever, hair loss and mouth sores.

Approximately 9 in 10 lupus patients are women, and it is most diagnosed between the ages of 15 and 45. Lupus also disproportionately affects Black, Latinx, Indigenous, Asian and Pacific Islander people. While most lupus patients can lead relatively normal lives, the disease can be life-threatening for approximately 10%-15% of sufferers. The leading causes of death in lupus patients are cardiovascular disease, kidney failure and serious infections.

There is currently no cure for lupus, but there are medications that address symptoms. However, the economic burden of lupus can be significant, with an average annual direct health care cost of $33,223. Annual economic productivity losses from missed work fall between $1,252 and $20,046.

“This research marks an important breakthrough, offering a mechanistic model of how EBV infection may trigger autoimmunity in lupus,” Hoang Nguyen, Ph.D., assistant vice president of research at the Lupus Research Alliance, said in a news release. “Dr. Robinson’s work not only deepens our understanding of EBV’s role in driving autoimmunity, it also opens the door to new strategies for treatment and prevention.”