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The following text has been machine translated from the German with no human editing.
The human immune system is a marvel comprising countless finely tuned components that interact with one another in just as countless processes, so that, in the end, we notice nothing. Ideally, we do not fall ill. Processes are constantly taking place in our bodies that eliminate damaged cells and halt, track down and kill viruses and bacteria. Most of the time this goes unnoticed, but sometimes we do feel it. Then our nose runs, our knees ache or a wound becomes inflamed. In people with a healthy immune system, however, such reactions are well balanced. The fever does not rise too high; inflammation remains localised and does not become too severe, so that it does not damage the surrounding tissue but only targets the foreign bodies at the site of the infection.
Sometimes, however, these processes become unbalanced. The immune system overreacts, and the processes that are actually meant to protect us spiral out of control. As a result, people whose immune systems react in this way often find themselves in mortal danger, facing the threat of severe acute or chronic inflammation of organs or autoimmune diseases such as rheumatism or multiple sclerosis.
Lorenz Thurner and his research group at the José Carreras Centre for Immunotherapy and Gene Therapy within the Department of Internal Medicine I at Saarland University have been researching such processes for a long time. Their focus is on a messenger substance called interleukin-1 and its antagonist, the interleukin-1 receptor antagonist (IL-1Ra). When interleukin-1 is released, an inflammatory response accompanied by fever is triggered to attack foreign substances such as viruses. IL-1Ra, on the other hand, blocks the binding sites for this messenger substance and thus inhibits the inflammatory response, preventing it from getting out of hand.
“Together with colleagues from other departments at the UKS and other hospitals, we have been able to investigate the role of IL-1Ra in greater detail over the past few years,” explains Professor Thurner. This is because, in some people, the body does not respond to IL-1Ra as intended: “The immune system produces antibodies against this antagonist, which it uses to attack it and thus neutralise it,” explains Professor Dr Christoph Kessel from the University of Münster, who researches such autoimmune and inflammatory processes at the Department of Paediatric Rheumatology and Immunology. As a result, the pro-inflammatory messenger substance interleukin-1 literally has a free rein, as it can now bind to its targets unhindered and trigger inflammation. The natural balance between the inflammatory response and its inhibition is disrupted.
The researchers led by Thurner and Kessel have known this to be the case for some time. However, exactly what happens to the IL-1Ra molecule had previously remained unknown. Now, with the help of a large, interdisciplinary team, they have been able to decipher this mechanism in COVID patients from the peak of the coronavirus pandemic and publish their findings in the prestigious journal *Nature Communications* (Publication 1, see below). “We were able to identify specific sites on IL-1Ra from people with severe COVID-19 at which an atypical biochemical change occurred,” report Evi Regitz and Natalie Fadle from Lorenz Thurner’s research group at the José Carreras Centre in Homburg.
This alteration in IL-1Ra is unknown to the adaptive immune system and leads to a breakdown in tolerance to IL-1Ra, thereby triggering an immune and ultimately an inflammatory cascade. The researchers now know exactly where these previously unknown vulnerabilities lie. “We also know that in these former patients who experienced severe COVID-19, the threshold for the occurrence of this atypical protein modification is much lower than in immunocompetent individuals,” adds Dr Bernhard Thurner, one of the study’s co-authors. “What we do not yet know, however, is whether COVID is the driver behind such a development or whether this reaction was already present in the patients’ immune systems beforehand. And why were those who fell ill more susceptible to such a reaction?” explains Christoph Kessel. This is a question that the now highly experienced team of scientists may be able to answer in the future.
The data on which the team based its findings proved particularly helpful for this latest study. Much of this data comes from the German NAPKON project, a consortium of previously decentralised national research activities. The ‘National Pandemic Cohort Network’, as it is officially known, was established in the wake of the 2020 coronavirus pandemic to centralise Covid-related research activities and make the resulting data available to all research institutions. “This data is worth its weight in gold. It enabled us to see that this imbalance in the immune system is a temporary effect. Over time, the level of antibodies against IL-1Ra in those affected decreases again,” says Lorenz Thurner, thereby emphasising the quality of this database.
This mechanism, which the research team has now been able to decipher in detail in Covid patients, is also evident in other diseases. In a short report published in parallel in the *Annals of the Rheumatic Diseases* (Publication 2, see below), Zanir Abdi (Senior Consultant in Rheumatology at UKS), Lorenz Thurner and Christoph Kessel also demonstrate this hyperphosphorylation in signalling molecules whose malfunction can trigger axial spondyloarthritis, a chronic inflammatory rheumatic disease.
The scientists’ findings are therefore of fundamental importance, extending far beyond a single disease such as Covid.
Original publications:
1) Lorenz Thurner, Natalie Fadle, Bernhard Thurner, Igor Kos, Moritz Bewarder, Evi Regitz, … , Marcin Krawczyk, Philipp Lepper, Christoph Kessel .* Autoantibodies to IL-1Ra and PGRN in severe COVID-19 are associated with inflammation-induced hyperphosphorylated antigen isoforms. Nat Commun 17, 4768 (2026). https://doi.org/10.1038/s41467-026-73316-5
2) Zanir Abdi, Natalie Fadle, Evi Regitz, Igor Age Kos, Onur Cetin, Klaus-Dieter Preuss, Marina Zaks, Philipp Klemm, Frank Neumann, Moritz Bewarder, Philipp B Staber, Bernhard Thurner, Christoph Kessel, Lorenz Thurner, Proinflammatory autoantibodies enhancing tumor necrosis factor and RANKL signaling in axial spondyloarthritis associate with hyperphosphorylated progranulin and osteoprotegerin, Annals of the Rheumatic Diseases, 2026, ISSN 0003-4967, https://doi.org/10.1016/j.ard.2026.04.008.
Further information:
Prof. Dr. Lorenz Thurner
Tel.: (06841) 1615001
Email: lorenz.thurner(at)uks.eu
Prof. Dr. Christoph Kessel
Tel.: (0251) 8358176
Email: christoph.kessel(at)uni-muenster.de
