Pathogenesis of membranous nephropathy: recent advances and future challenges.

International audienceOver the past few years, considerable advances have been made in our understanding of the molecular pathomechanisms of human membranous nephropathy, inspired by studies of Heymann nephritis, a faithful experimental model of this disease. This research led to the identification of neutral endopeptidase, the M-type receptor for secretory phospholipase A(2) (PLA(2)R1) and cationic bovine serum albumin as target antigens of circulating and deposited antibodies in alloimmune neonatal, adult 'idiopathic' and early-childhood membranous nephropathy, respectively. A genome-wide association study has provided further evidence for a highly significant association between PLA2R1 and HLA-DQA1 loci and idiopathic membranous nephropathy in patients of white ancestry. Additional antibody specificities for cytoplasmic antigens have also been identified, but their pathogenic role is uncertain. The time has come to revisit the spectrum of membranous nephropathies based on the newly identified antigen-antibody systems that should be considered as molecular signatures of the disease and that challenge the uniform histological definition. These signatures will soon have a major impact on patient care

Immunopathogenesis of membranous nephropathy: an update

International audienceMembranous nephropathy (MN) is a non-inflammatory 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. In the last 10 years, substantial advances have been made in the understanding of the molecular bases of MN, with the identification of several antigens and predisposing genes in children and adults. These ground-breaking findings already have a major impact on diagnosis and monitoring and to some extent on therapies. However, there is evidence that the disease is more complex and involves a variety of antigen-antibody systems and genes involved in immune response, progression, recovery, and protective mechanisms. We herein review these recent findings which open new perspectives of research. Understanding the complex pathogenesis of MN will offer many opportunities for future therapeutic interventions and will hopefully have a major impact on patient care. New insights into the molecular mechanisms of MN may also enlighten the pathogenesis of organ-specific autoimmune diseases