Lymphocyte repertoires in autoimmunity - dissecting rheumatic disease

The overall purpose of this project is to ‘finger print’ the immune reactions associated with autoimmune rheumatic diseases and use this knowledge for the development of novel and ultimately antigen-specific and curative therapies.We will study disease-associated autoimmunity in rheumatoid arthritis and ANCA-associated vasculitis.

We anticipate to identify the most prominent candidate autoantigens (including the precise epitopes recognized by B and T cells) as well as their corresponding lymphocyte repertoires.

Next, we will set up immune surveillance panels to screen autoreactive B and T cells and their clonal expansions in patients over time.

Ultimately, we aim to dissect the mechanisms by which specific T and B cell clones, alone or in combination cause disease manifestations (symptoms) by creating novel humanized mice to study transition from autoimmunity into autoimmune disease.A caveat to understanding human autoimmune disease has always been their gradual development over a long period of time.

An intriguing short cut to inflammatory disease resembling RA is the side effects sometimes developing in cancer patients treated with immune stimulatory check point inhibitors (ICI).

We will use our approaches to study to what extent ICI-induced arthritis is characterized by autoimmunity.My track record of identifying and studying candidate autoantigens and the involved B and T cell repertoires in patient samples will form a basis for this translational program.