Serum with phospholipase A2 receptor autoantibodies interferes with podocyte adhesion to collagen. (August 2014)

• Record Type: Journal Article
• Authors: Škoberne, Andrej; Behnert, Astrid; Teng, Beina; Fritzler, Marvin J.; Schiffer, Lena; Pajek, Jernej; Lindič, Jelka; Haller, Hermann; Schiffer, Mario
• Is Part Of: European journal of clinical investigation. Volume 44:Number 8(2014:Aug.)
• Page Start: 753
• Page End: 765
• Publication Date: 2014-08
• Subjects: Pathology -- Periodicals; Medical research -- Periodicals; 616.075
• DOI: 10.1111/eci.12292
• Languages: English
• ISSNs: 0014-2972

Abstract

<abstract abstract-type="main" id="eci12292-abs-0001"> <title>Abstract</title> <sec id="eci12292-sec-0001" sec-type="section"> <title>Background</title> <p>The majority of sera from patients with primary membranous nephropathy have autoantibodies against the M‐type phospholipase A2 receptor (PLA2R) which is expressed on human podocytes. The rabbit variant of PLA2R attaches to collagen type IV via the fibronectin type II domain, which is also present in the human variant of PLA2R.</p> </sec> <sec id="eci12292-sec-0002" sec-type="section"> <title>Design</title> <p>To assess whether the human PLA2R variant is also involved in attachment to collagen type IV, we conducted a cell adhesion assay on a collagen‐coated surface using PLA2R‐transfected and mock‐transfected human embryonic kidney (HEK) cells. To test the hypothesis that sera from patients containing anti‐PLA2R 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 <italic>in vitro</italic> expressing PLA2R.</p> </sec> <sec id="eci12292-sec-0003" sec-type="section"> <title>Results</title> <p>The HEK cell adhesion assay confirmed an enhanced attachment of PLA2R‐transfected cells to collagen type IV. We confirmed diminished podocyte adhesion in the presence of serum with anti‐PLA2R antibodies. The concentration of anti‐PLA2R antibodies correlated with proteinuria and to the degree of diminished adhesion of podocytes.</p> </sec> <sec id="eci12292-sec-0004" sec-type="section"> <title>Conclusions</title> <p>We demonstrated that serum of patients containing autoantibodies directed to PLA2R interferes with the ability of podocytes to attach to collagen type IV <italic>in vitro</italic>, providing evidence of a serum soluble pathogenic factor interfering with podocyte adhesion in membranous nephropathy.</p> </sec> </abstract>