Interferon alpha is an inflammatory mediator that can cause Sjögren’s syndrome, an autoimmune disease. This is revealed in a recent study carried out by the University Hospital Bonn together with the University of Bonn, the University of Edinburgh and Newcastle University. Their findings, which have been published in the journal “Lancet Rheumatology,” could make it easier in the medium term to develop drugs to fight this chronic condition.
Sjögren’s syndrome (also known as Sjögren’s disease) has a wide range of symptoms, from dry eyes and itchy skin to muscle and joint pain and chronic fatigue. The condition, an autoimmune disease, is in the group known as collagen disorders, which also includes lupus. With these diseases, the immune system attacks the body’s own structures inside organs and connective tissue, damaging them.
Sjögren’s syndrome mainly affects the exocrine glands, i.e. groups of cells that secrete water or mucus at the surface of the skin or inside the digestive tract, causing chronic inflammation and preventing them from doing their job properly. “This is why people living with the condition complain of low saliva production as well as dryness in their eyes and mucous membranes, among other things” explains Professor Rayk Behrendt, who was responsible for leading the Bonn-based part of the study. He is a researcher in the Institute of Clinical Chemistry and Clinical Pharmacology at the University Hospital Bonn and a member of the Life and Health Transdisciplinary Research Area and ImmunoSensation3 Cluster of Excellence at the University of Bonn.
Is dysregulated interferon alpha the culprit?
Just like with other collagen disorders, other parts of the body will also be damaged as time goes on, which is why doctors call it a “systemic disease.” The actual cause of the condition is unknown. “For a long time, however, there’s been the suspicion that an inflammatory mediator, specifically interferon alpha, is dysregulated in people affected by the disease,” Behrendt says. “Their bodies are producing too much of it, and this is what might be triggering the various symptoms.”
However, this hypothesis had not yet been truly proven—all that was known was that many people with Sjögren’s syndrome have an elevated level of interferon alpha. Yet many patients do not respond to treatments that weaken the effect of interferon alpha. The latest study has now provided an indication of why this is the case. “We studied the immune system of over 170 women and men with Sjögren’s disease very closely,” Behrendt explains.
A highly sensitive detection method
Except when it is fighting viral infections, the body normally only produces interferon alpha in tiny quantities, so the researchers used a new, ultra-sensitive method to detect individual molecules of it. They discovered that around 60 percent of patients had increased levels of interferon alpha, and it was precisely this 60 percent that also exhibited other characteristic differences in their immune system compared to their fellow patients. For example, the activity of certain immune genes—and thus the release of the corresponding proteins—was different. “We also found a molecule called TRIM21 in the other 40 percent, which the patients with elevated interferon alpha levels didn’t have,” says Dr. Ivana Jorgacevic, who carried out some of the experiments.
In experiments using mice, the researchers found that these heightened levels of interferon alpha were responsible for both the characteristically altered protein signature and the absence of TRIM21. The working groups also analyzed data on nearly 50,000 people from a UK database known as the UK Biobank. These individuals had all provided regular blood samples over many years, and around 250 of them were diagnosed with Sjögren’s syndrome and half of these received the diagnosis until partway through this period. “Analysis of the protein signature in the blood of these 250 patients showed that elevated interferon alpha had already been detected more than ten years before they developed the disease,” Jorgacevic explains. “Plus, they had no TRIM21.” Behrendt adds: “The combination of data from our own cohort, our analysis of the UK Biobank data and our studies on mice enabled us to demonstrate that there is a causal link between interferon alpha and characteristic changes in the immune system.”
Two different types of Sjögren’s syndrome
There therefore appears to be at least two different types of Sjögren’s syndrome. Although they differ in terms of both the amount of interferon produced in the body and a characteristic protein signature, they are clinically indistinguishable, at least initially. This “immune diversity” is not just of academic interest: “Now, for the first time, we can take treatments geared toward suppressing the interferon effect and trial them really specifically on patients with elevated interferon levels,” Behrendt says. “We might also find new approaches to treatment that will help at least a large percentage of patients over the long term.” The ImmunoSensation3 Cluster of Excellence works to understand precisely these kinds of immune diversity and is therefore now also keen to investigate why interferon alpha plays a role in some patients but not others.
Sponsorship
The University Hospital Bonn, the University Hospital Dresden, Heidelberg University Hospital, Cambridge University Hospitals, the University of Bonn, the University of Edinburgh, Newcastle University, University College Cork and the Warsaw-based company JJB Biologics were involved in the study. The work was funded by the German Research Foundation, the Precision Medicine Alliance Scotland, the Wellcome Trust and the Medical Research Council, which is part of UK Research and Innovation.
Publication
Forbes D, Jorgacevic I, Tarn J et al. Interferon-α as a precision medicine tool in Sjögren's disease: a cohort and experimental medicine study. The Lancet Rheumatology, 2026; DOI: 10.1016/S2665-9913(26)00038-X
Contact
Professor Rayk Behrendt
Institute of Clinical Chemistry and Clinical Pharmacology
University Hospital Bonn
Life and Health Transdisciplinary Research Area and ImmunoSensation3 Cluster of Excellence
University of Bonn
Phone: +49 228 287-51120
Email: behrendt@uni-bonn.de
