de Vries N.: Immunogenomic approaches to receptor specificity in the adaptive immune response, with a focus on rheumatic diseases

The research program “Adaptive immunomics” aims to unravel disease-associated adaptive immune responses in immune-mediated inflammatory disease. In these adaptive responses specificity is often encoded by only a few lymphocyte clones, each encoding a unique B- or T-lymphocyte receptor. To identify, track, monitor and selectively target these cell clones we developed molecular and bioinformatic approaches to fingerprint these receptors. Thus we identify and quantitatively monitor such clones over time, both in vivo and in vitro, and assess their tissue distribution, e.g. in diseased individuals. The goal is to develop tools that selectively downregulate disease-associated immune responses in autoimmune disease, thus providing the opportunity to intensify treatment of these diseases without the potential side-effects of standard immunosuppressive therapy, like infection or the slightly increased rates of tumor development. We think this approach will help to develop curative therapy in these diseases. Based on observed distribution of clones in time and place we are able to make inferences regarding the disease-relatedness of individual clones. By fine analysis of these clones
regarding cellular phenotype and genomic make-up in the different phases of the disease we aim to identify novel diagnostics, predictors and therapeutic targets in the diseases studied.

Many of these studies are performed in collaboration with local, national and international partners. Our primary focus is on autoimmune disease, e.g. rheumatoid artrhitis, multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, Crohn's disease and IgG4-related disease, and on related immune responses, e.g. anti-drug responses. Furthermore we also have very productive collaborations in highly diverse areas like infectious diseases e.g. in CMV, EBV, HIV and tuberculosis.