Nanoparticle-based autoantigen delivery to Treg-inducing liver sinusoidal endothelial cells enables control of autoimmunity in mice

Authors: Dario Didona, Christoph Hudemann, Holger Garn, Daria Krzikalla, Shu-Hung Wang, Julia Hinterseher, Karolin Volkmann, Alexandra Polakova, Anna Zakrzewicz, Simon Feldhoff, Ritva Tikkanen, Reinaldo Digigow, Wolfgang Pfützner, Antonio Santos, Christine L Zimmer, Maik Hahmann, Susanne Harnisch, Siegfried Rösch, Sandra Huguenin, Rüdiger Eming, Matthias Hahn, Franziska Schauer, Emiliano Antiga, Stefano Senatore, Roberto Maglie, Jörg Täubel, Kamran Ghoreschi, Katharina Meier, Farzan Solimani, Michael Sticherling, Lukas Sollfrank, Claudia Günther, Kerstin Steinbrink, Nina Magnolo, Erno van Schaick, Veronica Asnaghi, Frank S Zollmann, Johannes Pohlner, Julia Hummel, Rupert Sandbrink, Cristina de Min, Sabine Fleischer, Christian Möbs, Michael Hertl

Summary

Pemphigus is a rare but potentially life-threatening disease. It causes blisters to form on the skin, mouth and genitals. It can lead to the loss of body fluids and proteins. It is also associated with severe infections. Blisters are caused by ‘autoantibodies’ (misguided defence proteins in the immune system) that bind to a component of the skin called Dsg3. The autoantibodies are produced by specialized immune cells known as ‘B cells’ with the help of another group of immune cells called ‘T cells’. These cells play an important role in starting autoimmune responses.

In this study, we tried to block the effects of T cells in pemphigus. We did this using ‘nanoparticles’ to deliver pieces of Dsg3 to the liver. These nanoparticles have the potential to inhibit (or stop) the misdirected immune response. We carried out a study in Germany, Italy and the UK and gave increasing doses of Dsg3-loaded nanoparticles to a group of 17 patients with the disease. We found that the treatment was well-tolerated by the patients. They did not experience any severe side effects. We also found changes in the patients’ blood. This provided the first hints that T cells and activated B cells that promote inflammation could be blocked, leading to a decrease in pemphigus autoantibodies.

Our study findings suggest that Dsg3-loaded nanoparticles should be further developed. The aim would be to treat pemphigus, and maybe even other autoimmune diseases, in a safe and specific way.