Approximately 9% of the world population is affected by an autoimmune disease. These diseases often lead to debilitating morbidities that may have an enormous impact on the quality of life. Likewise, they frequently result in loss of employment and long-term care and treatment needs that represent a considerable cost for society. Most human autoimmune diseases are chronic, incurable conditions in which current interventions address the symptoms rather than causes of disease. Several autoimmune diseases, such as scleroderma or SLE, also have a profound impact on life expectancy, reflected in standardized mortality ratio’s that are similar and even higher than for breast cancer. The greatest challenge in the area of chronic human autoimmune diseases is to develop treatments that can induce permanent cure. This challenge can only be reached by combining new methods aiming to eradicate the disease-causing cells and/or pathways, with studies aiming to understand the processes that lead to the breach of immune tolerance and the emergence of autoimmunity.
Many autoimmune diseases are characterized by autoantibodies and are remarkably responsive to B-cell targeted therapies, demonstrating that the autoreactive B-cell is central to disease pathogenesis. Nonetheless, the selective and permanent elimination of the autoreactive B-cell, is not presently feasible due to a lack of specific markers and treatments. The aim of the project is to develop a vaccine that will allow the specific and long-lasting depletion of autoreactive B-cells, thereby inducing cure. This concept extends the remit of vaccines beyond infectious diseases and cancer, into the sphere of autoimmune disease. Using the well-defined autoimmune disease rheumatoid arthritis (RA) as prototype, we will study the RA-specific autoimmune response. Using recently developed technologies, we will identify autoreactive B-cells at several (pre)disease stages. Ultimately, we will design patient-tailored vaccines and perform a phase I trial to determine the feasibility of specifically depleting disease-causing B-cells.
This research will create the possibility for patient-tailored vaccines that can permanently eradicate auto-reactive B-cells in B-cell driven auto-immune diseases; diseases that are still incurable to date.
