For decades, the target antigen in patients with primary MN was unknown. In 2009, the group of David J. Salant and co-workers identified a 185-kDa glycoprotein as the major antigen of autoantibodies which were detected in 70 % of primary MN patients but not in patients suffering from secondary MN. The target protein was identified as M-type phospholipase A₂ receptor (PLA2R) by mass spectroscopy.¹

PLA2R is expressed on the surface of podocytes and binds soluble phospholipase A2. Although the exact pathogenic mechanisms causing primary MN are still under research, it is assumed that binding of the autoantibodies to PLA2R results in formation of in situ immune complexes in the area of the glomerular basement membrane. These may trigger local complement activation with overproduction of type IV collagen and laminin.² Destruction of the cytoskeleton may cause damage to the podocytes, which leads to an impaired filter function and the known symptoms (nephrotic syndrome): an increase of protein in the primary urine (proteinuria) accompanied by oedema and a compensatory increase in lipoprotein synthesis (see figure).³

¹Beck et al., N Engl J Med 361, 11-21 (2009)
²Ronco et Debiec, Nat Rev Nephr 8, 203-213 (2012)
³Ma et al., Semin Nephrol 33, 531-542 (2013)