WP4 - Technologies for monitoring the RA-associated immune state
This WP will provide a solid platform for immune monitoring. The tools, data and standard operating procedures (SOPs) developed within the WP will be applicable to diverse clinical trials, using different tolerising approaches performed by partners throughout the consortium (including industrial partners). Thus, we will put much emphasis on producing tools that are validated, consistent across laboratories and that will reveal distinct immune profiles that can be used as endpoints for a clinically tolerogenic state. These cellular signatures should be considered as “companion prognostics” – a set of markers that define a drug-induced state of immune tolerance – that could be used for drug development and licensing purposes.
Our work will focus on developing a suite of cutting edge platforms, technologies and analytical tools for identifying and monitoring tolerogenic signatures in immune cell subsets most closely associated with a clinical state of deep and stable (drug free) remission. For pragmatic reasons, peripheral blood mononuclear cells will provide the “substrate” for our analyses, although we will also study extra-articular tissues, such as lymph nodes, as well as synovial fluid and tissue derived cells. Our approach will be informed by tolerance phenotypes and functional assays developed by the Partners, and will exploit state-of-the-art tools for analysis of autoreactive effector T and B cell populations in samples from MHC class II genotyped donors.
Our specific goals are as follows:
To design and implement immune cell profiles for deep functional phenotyping and for defining tolerogenic signatures
To develop scalable platforms
To test the impact of tolerising therapies on tolerogenic signatures
To validate immune phenotypes in relation to clinical outcome