A groundbreaking new study has revealed that the Epstein-Barr virus (EBV), long known as the cause of infectious mononucleosis or “mono,” may also be a significant driver of lupus, a chronic autoimmune disease. This discovery sheds light on the mysterious origins of lupus and opens promising avenues for targeted therapies and preventative measures, including the development of vaccines.
EBV is a type of herpesvirus that infects approximately 94 percent of the global adult population. While most people carry the virus without severe symptoms, EBV is notorious for causing mono, characterized by fever, sore throat, and fatigue. For years, scientists have speculated that EBV could play a role in triggering lupus, but this hypothesis was primarily supported by anecdotal evidence and epidemiological associations rather than direct proof. Lupus is a complex autoimmune condition in which the immune system mistakenly attacks healthy tissues and organs, leading to inflammation and damage in areas such as joints, skin, kidneys, heart, lungs, blood, and the nervous system. Despite affecting at least five million individuals worldwide, the underlying causes of lupus have remained elusive.
The new research, conducted by a team at Stanford University and published in the journal Science Translational Medicine, provides the first concrete evidence linking EBV infection to the development and persistence of lupus. Using advanced single-cell sequencing techniques specifically tailored to detect EBV-infected cells, the researchers examined blood samples from individuals with lupus and healthy controls to identify how the virus interacts with the immune system in affected patients.
Central to the study are B cells, a subset of white blood cells responsible for producing antibodies to fight infections. EBV is known to infect B cells, but studying its role in autoimmune diseases has been difficult because only a tiny fraction of B cells—estimated at one in a thousand or fewer—are actually infected. The Stanford team overcame this challenge by developing a novel, EBV-specific single-cell sequencing method that allowed them to isolate and analyze these rare infected B cells.
The researchers discovered that people with lupus have about 25 times more EBV-infected B cells in their blood compared to healthy individuals. More importantly, EBV was found to “reprogram” these infected B cells, altering their function in a way that promotes autoimmunity. Rather than defending the body against pathogens, these EBV-infected B cells begin to present the body’s own molecules as foreign, triggering an immune response against the self. This mistaken identity fuels the chronic inflammation characteristic of lupus.
Further analysis showed that the antibodies produced by these infected B cells often mistakenly target components of the body’s own cells, leading to tissue damage. This finding provides a mechanistic explanation for how EBV infection could trigger and sustain lupus, linking the presence of the virus directly to the production of harmful autoantibodies.
The study’s findings have been hailed as “transformational” by experts in the field. William Robinson, a Stanford rheumatologist and co-author of the study, emphasized the potential implications for treatment and prevention. “We think that this is a transformational discovery,” Robinson said, suggesting that understanding the virus’s role in lupus could pave the way for new vaccines designed to prevent the disease.
Supporting this view, immunologist Akiko Iwasaki of Yale University, who was not involved in the study, described the research as “groundbreaking.” Iwasaki highlighted how the paper provides a much-needed mechanistic link between EBV and lupus, strengthening the case for developing EBV vaccines as a strategy to prevent autoimmune diseases.
The connection between EBV and autoimmunity is not entirely new. In 2022, a study co-authored by Robinson revealed that EBV also plays a role in multiple sclerosis (MS), another autoimmune disorder. That research showed that EBV primes the immune system to attack the nervous system, a process with strong parallels to what is now observed in lupus. Epidemiological data have also long indicated that people with lupus frequently exhibit high levels of antibodies against EBV proteins, and that viral reactivation often coincides with lupus flare-ups.
Beyond autoimmune diseases, EBV has been linked to certain cancers, including nasopharyngeal and stomach cancers. The virus’s ability to infect billions of B cells and manipulate their function has made it a focus of intense research. However, the new study is unique in its ability to pinpoint how EBV-infected B cells contribute specifically to autoimmune pathology.
Despite the excitement, some experts urge caution. George Tsokos, a rheumatologist