Serum with phospholipase A 2 receptor autoantibodies interferes with podocyte adhesion to collagen

Background The majority of sera from patients with primary membranous nephropathy have autoantibodies against the M ‐type phospholipase A 2 receptor ( PLA 2 R ) which is expressed on human podocytes. The rabbit variant of PLA 2 R attaches to collagen type IV via the fibronectin type II domain, which is also present in the human variant of PLA 2 R . Design To assess whether the human PLA 2R variant is also involved in attachment to collagen type IV , we conducted a cell adhesion assay on a collagen‐coated surface using PLA 2 R ‐transfected and mock‐transfected human embryonic kidney ( HEK ) cells. To test the hypothesis that sera from patients containing anti‐ PLA 2 R antibodies interfere with the adhesion of podocytes to collagen, we performed cell adhesion assays on a collagen type IV ‐coated surface using positive and negative serum samples from patients and cultured human podocytes in vitro expressing PLA 2 R . Results The HEK cell adhesion assay confirmed an enhanced attachment of PLA 2R‐transfected cells to collagen type IV . We confirmed diminished podocyte adhesion in the presence of serum with anti‐ PLA 2 R antibodies. The concentration of anti‐ PLA 2 R antibodies correlated with proteinuria and to the degree of diminished adhesion of podocytes. Conclusions We demonstrated that serum of patients containing autoantibodies directed to PLA 2 R interferes with the ability of podocytes to attach to collagen type IV in vitro , providing evidence of a serum soluble pathogenic factor interfering with podocyte adhesion in membranous nephropathy.