Stinne Ravn Greisen

Project title

Autoantibodies in Translational  Medicine -from Diagnostic Tools  to Pathogenic Drivers

What is your project about?

Autoimmune diseases occur when the immune system attacks the body's own tissues. These diseases often have autoantibodies that target the body's own proteins. In conditions such as systemic sclerosis, lupus, and Sjögren’s disease, these autoantibodies are directed against proteins located inside cells. However, it has long been assumed that autoantibodies cannot enter living cells and therefore they only serve as markers of disease.      

My project challenges this assumption by investigating whether autoantibodies targeting intracellular proteins can actively drive disease dprogression. Specifically, I will examine how these autoantibodies enter living cells, bind to their target proteins, and activate the immune system from within. If confirmed, this would suggest that autoantibodies are not only diagnostic markers, but direct drivers of disease progression and tissue damage. These findings could fundamentally change our understanding of autoimmune diseases and pave the way for new and more targeted treatment strategies.

How did you become interested in your particular field of research?

I have always been fascinated by how autoimmune diseases arise and progress. This interest led me to question why autoantibodies targeting different proteins inside cells are associated with distinct diseases and clinical manifestations. At the same time, I observed that patients often improved when the levels af these disease-specific autoantibodies declined. This made me ask a fundamental question: could autoantibodies targeting intracellular proteins play a direct and active role in disease development?  

Our preliminary findings suggest that they can. We have found evidence that certain autoantibodies are able to enter living cells and influence key biological processes. If this mechanism proves to be relevant across multiple diseases, it would challenge a fundamental assumption in immunology and reshape our understanding of autoantibodies role in disease. This combination of a clinically important question and the opportunity to push the boundaries of our biological understanding drives my research.

What are the scientific challenges and perspectives in your project?

The main scientific challenge of this project is that it investigates an idea that challenges a long-standing paradigm in immunology. For decades, it has been assumed that autoantibodies cannot enter living cells and therefore can only affect processes outside the cell. However, my preliminary findings suggest that certain disease-associated autoantibodies can cross the cell membrane, bind to intracellular proteins, and trigger immune activation from within.  

If this mechanism can be demonstrated across multiple autoimmune diseases, it would fundamentally change our understanding of what autoantibodies are capable of and the role they play in disease development. The implications extend far beyond connective tissue diseases and may be relevant to a wide range of autoimmune, neurological, and endocrine disorders. Ultimately, this knowledge could pave the way for new therapeutic strategies aimed at blocking pathogenic autoantibodies or preventing their entry into cells.

What is your estimate of the impact, which your project may have to society in the long term?

Autoimmune diseases affect millions of people worldwide and often require lifelong treatment. If we can demonstrate that autoantibodies actively drive disease by entering living cells, it could pave the way for more targeted therapies that address the underlying cause of disease rather than simply controlling its symptoms.      

The implications extend far beyond autoimmune diseases. By understanding how antibodies gain access to living cells, we may uncover principles that can be harnessed to develop a new generation of therapeutic antibodies. This could enable the targeting of disease-driving proteins inside cells, opening new treatment opportunities in areas such as cancer, autoimmune diseases, and other conditions with unmet medical needs.

Which impact do you expect the Sapere Aude programme will have on your career as a researcher?

I am both proud and grateful to receive the Sapere Aude: DFF Research Leader grant. It is a tremendous recognition of the research I have conducted so far and of the ideas I aspire to pursue in the future. The grant provides a unique opportunity to expand my research group and pursue ambitious research questions with the potential to challenge established concepts in immunology. I look forward to further developing a dynamic and ambitious research environment where curiosity, collaboration, and the development of the next generation of researchers go hand in hand.