Francesca Faustini

Autoimmune diseases are chronic incurable diseases caused by the interplay of genetic and environmental factors which result in a dysregulation of the immune system, where B cells contribute by presenting autoantigens to T cells and by producing autoantibodies.  This has made B-cell depletion treatment (BCTD) a suitable therapeutic strategy for autoimmunity. Today, new modalities of BCTD using engineered T cells (CAR T) and T-cell engagers may offer advantages over protein-based approaches used in the last decades (eg, monoclonal antibodies) ensuring a deeper tissue-level depletion correlating with a better clinical response. This study, conducted at Karolinska Institutet and Karolinska University Hospital, aims to investigate the mechanistic process of immune resetting following BCTD in systemic lupus erythematosus, idiopathic inflammatory myopathies, and systemic sclerosis. Cellular and molecular analyses of blood and lymph node tissues before and after treatment comparing three BCDT modalities (CAR T, T-cell engagers, monoclonal antibodies against B cells) will be performed in relation to the clinical effects of these treatments, using immune phenotyping, single cell transcriptomics, and spatial proteomic characterization. The knowledge generated from this project will ultimately help in personalized medicine, to make clinically relevant decisions based on molecular characterization of each patient’s disease phenotype.