Neuronal Proteins as Antigenic Targets in Membranous Nephropathy

The discovery of new target antigens in membranous nephropathy (MN) has revealed new disease phenotypes and, in some cases, has suggested mechanisms of disease shared by two concurrent autoimmune diseases. Subject of Review: Several recent reports and an accompanying editorial describe the association of anti-contactin-1 (CNTN1) autoantibodies of the IgG4 subclass with a novel subtype of MN that co-occurs with a form of chronic inflammatory demyelinating polyradiculoneuropathy caused by anti-CNTN1 antibodies. CNTN1, the cellular source of which is still undetermined, is identified as the target antigen in the kidney since it is present within glomerular subepithelial deposits and anti-CNTN1 IgG4 antibodies can be eluted from the corresponding kidney biopsy tissue. Second Opinion: These new reports reinforce recent findings that many proteins targeted in several other types of primary and secondary MN are proteins whose expression is shared by podocytes and neurons. While complement-mediated podocyte damage represents a well-established paradigm in the pathogenesis of MN, interference with the normal functions of these shared proteins by autoantibodies should be considered as another potential mechanism of glomerular injury to be explored in future research.