Autoimmune rheumatologic diseases
In autoimmune diseases, inflammation is often limited to specific target tissues, but within tissues, multiple sites can be affected. An important outstanding question is whether affected sites are infiltrated with the same (pathogenic) T cell clones and whether these clones persist over time. In Juvenile Idiopathic Arthitis it is possible to analyze large number of cells derived from the site of inflammation, i.e. inflamed joints. Here, we performed CyToF analysis and T cell receptor (TCR) sequencing to study immune cell composition and (hyper)expansion of inflamed joint-derived T cells. Samples were taken from different joints affected at the same time, and joints that were affected multiple times during the relapsing remitting course of the disease. CyTOF analyses revealed that the composition and functional characteristics of the immune infiltrates are strikingly similar between joints within one patient. Furthermore we observed a strong overlap between dominant T cell clones, especially Treg, in inflamed joints affected at the same time. Some of the most dominant clones could also be detected in circulation. Dominant Treg and Teff cell clones were found to persist over time and to expand during relapses, even after full remission of the disease. Finally, despite having little overlap between patients for the exact TCR sequence, we found several shared immune fingerprints, based on sequence motifs.. These data suggest that in autoimmune disease there is (dominant) auto-antigen driven expansion of both Teff and Treg clones that are highly persistent and (re)circulating. Therefore these dominant clones can be interesting therapeutic targets.