Antigen-specific treatments to target autoimmune kidney diseases

Chronic kidney disease (CKD) affects around 10% of the population worldwide and is associated with significant overall and cardiovascular mortality. CKD is a heterogeneous group of disorders characterized by alterations in kidney structure and function and is progressive in nature. Autoimmune diseases are a common cause of CKD and responsible for its most aggressive and progressive forms, mainly in younger patients. Autoantibodies play major pathogenic roles in most of these disorders and multiple disease-specific target antigens have been identified circumstances that have shifted treatment strategies from largely unspecific immunosuppression towards B and plasma cell-targeted therapies. However, such treatments still involve broad immunosuppression with potentially severe adverse effects. Hence, there is a huge gap between the increasing insights into the immune mechanisms and pathogenic role of autoantibodies against cellular antigens on the one side and the currently available treatments with limited specificity on the other side. The vision of AUTO-TARGET is the development and experimental implementation of pathogenesis-based and antigen-specific treatments for autoimmune diseases of the kidney. The objectives are (1) to identify and characterize novel molecular targets on autoantibody-secreting cells, (2) to target autoreactive B and plasma cells using nanobody-based compounds, and (3) to engineer chimeric autoantibody receptor NK and T cells for the treatment of different autoimmune diseases of the kidney. AUTO-TARGET thereby revolves around a highly translational approach, combining target identification and characterization in patients with autoimmune kidney diseases with unique in vitro and in vivo systems to model disease and validate therapeutics. These translational studies pave the way for more specific, less toxic treatments and thus may implicate a huge step forward for the large and growing population of patients with kidney disease.