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Serum with phospholipase A 2 receptor autoantibodies interferes with podocyte adhesion to collagen
Author(s) -
Škoberne Andrej,
Behnert Astrid,
Teng Beina,
Fritzler Marvin J.,
Schiffer Lena,
Pajek Jernej,
Lindič Jelka,
Haller Hermann,
Schiffer Mario
Publication year - 2014
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.12292
Subject(s) - podocyte , autoantibody , receptor , adhesion , phospholipase , chemistry , microbiology and biotechnology , medicine , endocrinology , immunology , biology , biochemistry , antibody , enzyme , kidney , proteinuria , organic chemistry
Abstract 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.