Discoveries in Bonn, Edinburgh and Newcastle could boost pharmaceutical research.
Interferon alpha is an inflammatory mediator that can cause the autoimmune disease Sjogren’s syndrome. This was revealed in a recent study carried out by Bonn University Hospital in collaboration with the University of Bonn, the University of Edinburgh and the University of Newcastle. Their findings, published in the journal Lancet Rheumatology, could facilitate the development of drugs to combat this chronic disease in the medium term.
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. This condition is an autoimmune disease and belongs to a group known as collagen diseases, which also includes lupus. In these diseases, the immune system attacks and damages the body’s own internal structures, such as organs and connective tissue.
Sjögren’s syndrome primarily affects the exocrine glands, a group of cells that secrete water and mucus on the surface of the skin or inside the gastrointestinal tract, causing chronic inflammation and interfering with the proper functioning of the exocrine glands. “This is why people living with this condition complain, among other things, of decreased saliva secretion and dryness of the eyes and mucous membranes,” explains Professor Lake Behrendt, who led the Bonn-based research part. He is a researcher at the Institute of Clinical Chemistry and Clinical Pharmacology at the University Hospital Bonn and a member of the Interdisciplinary Research Area of Life and Health and the Immune Senses 3 Cluster of Excellence at the University of Bonn.
Could dysregulated interferon alpha be the culprit?
Doctors call this a “systemic disease” because, like other collagen diseases, other parts of the body are damaged over time. The actual cause of this condition is unknown.
However, there has long been a suspicion that inflammatory mediators, particularly interferon alpha, may be dysregulated in people affected by the disease. Their bodies produce too much of it, and this can cause a variety of symptoms. ”
Professor Lake Behrendt, Researcher, Institute of Clinical Chemistry and Clinical Pharmacology, Bonn University Hospital
However, this hypothesis has not yet been truly proven, and all that was known was that many people with Sjögren’s syndrome have elevated levels of interferon alpha. However, many patients do not respond to treatments that reduce the effects of interferon alpha. The latest research reveals why. “We studied the immune systems of more than 170 women and men with Sjögren’s disease very closely,” Behrendt explains.
Highly sensitive detection method
The researchers used a new ultra-sensitive method to detect individual molecules of interferon alpha, because the body normally produces only small amounts of it, except when fighting a viral infection. They found that about 60 percent of patients had elevated levels of interferon alpha. And they found that just this 60 percent also showed other characteristic differences in their immune systems compared to other patients. For example, the activity of certain immune genes, and hence the release of the corresponding proteins, was different. “We also found a molecule called TRIM21 in the remaining 40%, but it was absent in patients with elevated interferon-alpha levels,” says Dr. Ivana Giorgasevic, who conducted part of the experiment.
In experiments with mice, researchers found that these elevated levels of interferon-alpha were responsible for both the characteristically altered protein signature and the absence of TRIM21. The working group also analyzed data on around 50,000 people from a UK database known as the UK Biobank. All of these people had given blood samples regularly over the years, and about 250 of them were diagnosed with Sjögren’s syndrome, half of them by the middle of this period. “When we analyzed the protein signatures in the blood of these 250 patients, we found that elevated levels of interferon alpha were already detected more than 10 years before they developed the disease,” explains Dr. Giorgasevic. “Furthermore, there was no TRIM21,” Behrendt added. “By combining data from our own cohort, analysis of UK Biobank data, and studies on mice, we were able to demonstrate a causal relationship between interferon alpha and characteristic changes in the immune system.”
Two different types of Sjögren’s syndrome
Therefore, it appears that there are at least two different types of Sjögren’s syndrome. They differ both in the amount of interferon produced in the body and in their characteristic protein features, but are clinically indistinguishable, at least initially. This “immune diversity” is not only of academic interest. “Now, for the first time, we can take a therapy that aims to inhibit the effects of interferon and actually test that therapy in patients with elevated interferon levels,” Behrendt says. “We may also find new treatments that help at least the majority of patients in the long term.” The ImmunoSensation3 Cluster of Excellence is working to understand exactly this kind of immune diversity, and is therefore now also hard at work investigating why interferon alpha plays a role in some patients but not others.
Participating institutions and funding secured: Bonn University Hospital, Dresden University Hospital, Heidelberg University Hospital, Cambridge University Hospital, University of Bonn, University of Edinburgh, University of Newcastle, University College Cork and the Warsaw-based company JJB Biologics were involved in the study. The study was funded by the German Research Foundation, Precision Medicine Alliance Scotland, the Wellcome Trust and the Medical Research Council, which is part of Research and Innovation UK.
sauce:
Reference magazines:
Forbes, D. Others. (2026). Interferon-alpha as a precision medicine tool in Sjögren’s disease: a cohort and experimental medicine study. lancet rheumatology. DOI: 10.1016/S2665-9913(26)00038-X. https://www.sciencedirect.com/science/article/pii/S266599132600038X
