The discovery began with a puzzle. For years, doctors knew that people with Sjögren's syndrome often had high levels of a molecule called interferon alpha in their blood. But they could not prove whether that molecule was actually causing the disease—or just a harmless byproduct of it.
Now, a team of researchers from University Hospital Bonn, working alongside scientists from the University of Bonn, the University of Edinburgh, and Newcastle University, has found an answer. Their study, published in the journal Lancet Rheumatology, shows that interferon alpha does indeed trigger Sjögren's syndrome in about 60 percent of patients.
Sjögren's syndrome is an autoimmune disease that affects the glands producing saliva, tears, and other moisture in the body. Patients experience dry eyes, dry mouth, and often exhaustion, joint pain, and skin problems. The immune system mistakenly attacks the body's own tissues, causing chronic inflammation that can damage glands and, over time, other organs. Professor Rayk Behrendt from University Hospital Bonn, who led the study, explains that this is why people with the condition often struggle with basic functions like swallowing or producing tears.
The researchers studied more than 170 women and men with Sjögren's disease using a powerful new detection method sensitive enough to find individual molecules of interferon alpha. They found that roughly 60 percent of patients had elevated levels of this molecule, and these same patients shared other distinctive patterns in their immune systems.
The team also uncovered something interesting about the remaining 40 percent. These patients had a molecule called TRIM21 that the other group lacked. When the researchers tested this connection in mice, they confirmed that high interferon alpha levels produced exactly the immune patterns seen in the 60 percent group—and the absence of TRIM21.
The implications go beyond diagnosis. The researchers also examined data from nearly 50,000 people in the UK Biobank, a large health database where participants give blood samples over many years. Among them, about 250 people were diagnosed with Sjögren's syndrome, with roughly half receiving their diagnosis during the study period. The blood samples revealed that elevated interferon alpha was already present more than 10 years before these individuals developed any symptoms.
"The combination of data from our own cohort, our analysis of the UK Biobank data, and the experiments in mice shows clearly that dysregulated interferon alpha plays a key role in a large proportion of patients," Behrendt says.
This finding offers real hope. If researchers can develop drugs that either block interferon alpha or restore the balance of TRIM21, they might be able to prevent or treat the disease in the majority of patients who are affected by this specific mechanism. The path from discovery to treatment takes time, but for the millions of people living with Sjögren's worldwide, this study marks a meaningful turning point.