A new study has finally nailed down what links Epstein-Barr virus (EBV) – a pathogen that over 95 percent of adults worldwide have been infected with – to lupus, solving a long-standing mystery.

Lupus, also called systemic lupus erythematosus or SLE, is a chronic autoimmune disease in which the immune system attacks the body’s own tissue, and can result in a wide variety of symptoms ranging from skin rashes and fatigue to severe damage to the lungs and kidneys. Actress and singer Selena Gomez was diagnosed with lupus in her early 20s, and received a kidney transplant back in 2017 due to the effects of the disease.

She’s just one of at least 5 million people estimated to be affected by lupus, the causes of which are poorly understood. While genetics might be one possible trigger, it’s long been suspected that EBV – the same virus that causes glandular fever – is also linked to the condition.

What scientists had trouble with was figuring out exactly how the two were linked – what were the mechanisms that led one to trigger the other? 

That’s where the new study, led by researchers at Stanford Medicine, came in. They developed a novel technique for identifying B cells infected by EBV and which genes within these cells were being expressed. 

B cells are white blood cells that play a key role in the body’s immune system – producing antibodies. But they have another important role too, presenting antigens – molecular "red flags" on foreign entities like viruses that trigger an immune response – to other immune cells, which scales up the response from the body’s immune system. Around 20 percent of B cells are also designed to target our own tissues, but they usually lie inactive.

The team’s technique revealed that in healthy individuals carrying EBV, fewer than 1 in 10,000 of their B cells were infected with the virus. In people with lupus, that rose to 1 in 400. 

Their findings also revealed that in these infected cells, EBV could cause them to express a “molecular switch” gene, activating a cascade of pro-inflammatory gene expression that led a B cell to transform into its antigen-presenting self. In turn, this activated other immune cells to join the response gang – including those otherwise sleepy self-attacking B cells, as well the appropriately named killer T cells that destroy the body’s own tissues.

This is what causes lupus, the researchers conclude, and they also suspect the same mechanism could be involved in other autoimmune diseases like multiple sclerosis, which has also been linked to EBV.