Membranous nephropathy (MN) is a paradigm of organ-specific autoimmune disease which affects the kidney glomerulus, resulting in the formation of immune deposits on the outer aspect of the glomerular basement membrane, complement-mediated proteinuria, and severe renal failure in 30% of patients. We have recently identified 2 causative antigens (neutral endopeptidase and cationic bovine serum albumin) in children, and 2 major predisposing genes HLA-DQA1 and PLA2R1 coding for another antigen in adult MN. However, there is evidence that the disease is more complex and involves several antigen-antibody systems and genes involved in immune response, progression and recovery.
We are developing novel technological approaches such as immunopeptidomics, and exploring new pathophysiological and therapeutic concepts with 3 major objectives: 1. Identify the immune response targets (epitopes); 2. Investigate trigger genes and other relevant genes involved in autoimmunity or disease progression; 3. Revisit complement-related innate immunity by genetic and pharmacological approaches.