Selective CAR-T cell mediated B cell depletion suppresses interferon signature in SLE

Applying advanced molecular profiling together with highly specific targeted therapies offers the possibility to better dissect the mechanisms underlying immune mediated inflammatory diseases such as systemic lupus erythematosus (SLE) in humans. Here we apply a combination of single cell RNA sequencing and T/B cell repertoire analysis to perform an in-depth characterization of molecular changes in the immune-signature upon CD19 CAR T cell-mediated depletion of B cells in SLE patients. The resulting datasets do not only confirm a selective CAR T cell-mediated reset of the B cell response, but simultaneously reveal consequent changes in the transcriptional signature of monocyte and T cell subsets that respond with a profound reduction in type 1 interferon signaling. Our current data thus provide evidence for a causal relationship between the B cell response and the increased interferon signature observed in SLE and additionally demonstrate the usefulness of combining targeted therapies and novel analytic approaches to decipher molecular mechanisms of immune-mediated inflammatory diseases in humans.