International doctoral programme on specific autoimmune diseases

The doctoral network “IgG4-TREAT - Systematic study of IgG4-autoimmune diseases to develop new treatment strategies” funded by the European Union within the framework of Marie Sklodowska-Curie Actions, is now starting the recruitment phase. The European consortium involves 13 academic research institutions, including the Faculty of Medicine at Kiel University (CAU) and the University Hospital Schleswig-Holstein (UKSH), as well as 3 companies from 7 countries. Interested young researchers from the life sciences can now apply for one of a total of ten doctoral projects in Germany (Kiel, Berlin), Austria (Vienna), France (Paris), the Netherlands (Leiden, Maastricht, Amsterdam), Greece (Athens), Italy (Pisa) or Turkey (Istanbul). The research network has a total of 2.63 million euros at its disposal until the studies are completed in 2027.

The overarching research topic is autoimmune diseases with organ-specific autoantibodies of a specific subtype, the IgG4 isotype. These include, for example, inflammations of the peripheral nervous system (immune neuropathies), subtypes of the nerve-muscle disease myasthenia gravis and autoimmune diseases of the central nervous system (autoimmune encephalitides) as well as certain blistering skin diseases and glomerular kidney diseases. "Our consortium assumes that common pathomechanisms are present in all of these diseases, the investigation of which also opens up shared treatment options," explains Kiel project leader PD Dr. Frank Leypoldt, one of the heads of the Neuroimmunology working group at the Institute of Clinical Chemistry at the UKSH and a member of the Cluster of Excellence "Precision Medicine in Chronic Inflammation" (PMI) "The diseases we are talking about are rare in themselves, but together they are a relevant group."

Common denominator: autoantibodies of the type IgG4

The cross-organ, joint consideration of these different IgG4 autoimmune diseases is the research consortium’s main topic. The diseases are clinically severe, sometimes difficult to diagnose and hard to treat. They affect various organs and have therefore not yet been considered in an overarching way. "The common denominator of all these diseases, however, are the IgG4 type antibodies," says Leypoldt. Until now, these antibodies were actually considered anti-inflammatory, as they activate other components of the immune system significantly less than other isotypes. The problem is that they still bind with high strength to their respective antigen, an endogenous protein, and block its function. "We have been observing this phenomenon in completely different organ systems, in the skin, kidney, brain and peripheral nerves. We want to understand this and exploit it therapeutically. Perhaps solutions can be found that can be applied across the board," explains the expert on autoimmune brain diseases.

Innovative education at different locations

The programme focuses on training and networking young researchers in the field of IgG4 antibody-mediated diseases. Laboratories and institutes with complementary expertise and resources have been brought together to ensure a balanced portfolio of expertise from different European countries for the educational network. An integral part of the Marie Sklodowska Curie Doctoral Networks is that the international doctoral candidates not only conduct research with their project at their location, but also rotate to other laboratories for three to six months in a structured manner. "In the partner labs, which work on other aspects of the initial question, they can train new techniques and broaden their horizons," Leypoldt emphasises. Together with neuroimmunologist Professor Klaus-Peter Wandinger, bioinformatician Dr. Daniela Esser and expert in neurogenetics and molecular neurobiology Professor Gregor Kuhlenbäumer, he is leading the Kiel research project, in which, among other things, immune cells in the cerebrospinal fluid of patients with autoimmune encephalitis are being studied. Here, the latest molecular biological investigation methods like single cell sequencing are being used to find out why the immune cells permanently produce IgG4 autoantibodies. By analysing existing gene data, they will examine whether there are abnormalities at the genetic level that are also found in other IgG4 autoimmune diseases.