Selective CAR T cell–mediated B cell depletion suppresses IFN signature in SLE
Artur Wilhelm, David Chambers, Fabian Müller, Aline Bözec, Ricardo Grieshaber‐Bouyer, Thomas Winkler, Dimitrios Mougiakakos, Andréas Mackensen, Georg Schett, Gerhard Krönke
Abstract
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-Seq 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 patients with SLE. The resulting data sets 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 I IFN signaling. Our current data, thus, provide evidence for a causal relationship between the B cell response and the increased IFN signature observed in SLE and additionally demonstrate the usefulness of combining targeted therapies and analytic approaches to decipher molecular mechanisms of immune-mediated inflammatory diseases in humans.