Inflammatory rheumatic disease - importance and contribution of B and T cell subsets
Today inflammatory rheumatic diseases like RA (rheumatoid arthritis) can be treated with different biological therapies including those who target B and T cells. Still, we do not understand precisely how T and B cell subsets contribute to disease. In the cellular immunology/rheumatology group we aim to
a) Identify disease-specific T and B cells from blood and synovial fluid of well-characterized RA patients.
b) Investigate the functionality of different lymphocyte subsets like antigen-specific T cells, CD28null T cells and regulatory T cells to rheumatic disease.
c) Follow RA patients undergoing B and T cell directed therapy to study mechanisms of action in aspect to e.g. antigen-specificity and cellular compartments.
We are studying T and B cells based on patient samples from the rheumatology clinic. Our main method is flow cytometry. We do cell sorting for functional studies (in vitro cultures) and epigenetic analysis (FOXP3, IFNg, IL-17) of T cell subsets (e.g. Treg and CD28null), and extensive characterization and functional analysis of T and B cell subsets by multi parameter flow (9-colours) including intracellular cytokine staining and degranulation assays. Our RA patient cohort (n=300) has been characterized based on serology and genotype, and ongoing studies focus on finding antigen-specific lymphocytes. We also work closely with clinical fellows to include relevant clinical parameters in our analysis. In collaborative efforts within the FP6 EU-project (Autocure) and the FP7 EU project (Masterswitch) we are dissecting specific immune responses at different disease stages and from different cellular compartments. Our favourite candidate autoantigens are derived from extracellularly modified type II collagen, alpha-enolase, fibrinogen and vimentin.