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Membranous nephropathy: from models to man
Laurence H. Beck Jr., David J. Salant
Laurence H. Beck Jr., David J. Salant
Published June 2, 2014
Citation Information: J Clin Invest. 2014;124(6):2307-2314. https://doi.org/10.1172/JCI72270.
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Membranous nephropathy: from models to man

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Abstract

As recently as 2002, most cases of primary membranous nephropathy (MN), a relatively common cause of nephrotic syndrome in adults, were considered idiopathic. We now recognize that MN is an organ-specific autoimmune disease in which circulating autoantibodies bind to an intrinsic antigen on glomerular podocytes and form deposits of immune complexes in situ in the glomerular capillary walls. Here we define the clinical and pathological features of MN and describe the experimental models that enabled the discovery of the major target antigen, the M-type phospholipase A2 receptor 1 (PLA2R). We review the pathophysiology of experimental MN and compare and contrast it with the human disease. We discuss the diagnostic value of serological testing for anti-PLA2R and tissue staining for the redistributed antigen, and their utility for differentiating between primary and secondary MN, and between recurrent MN after kidney transplant and de novo MN. We end with consideration of how knowledge of the antigen might direct future therapeutic strategies.

Authors

Laurence H. Beck Jr., David J. Salant

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Figure 1

PLA2R staining in normal and MN glomeruli, and EM of typical subepithelial deposits in MN.

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PLA2R staining in normal and MN glomeruli, and EM of typical subepitheli...
(A) IF staining of a normal glomerulus demonstrating PLA2R expression throughout the podocyte (red). Cell nuclei were counterstained with Hoechst dye (blue). (B) A higher-magnification view of a normal glomerulus shows podocytes, labeled with nuclear WT1 (green), that exhibit PLA2R (red) staining diffusely throughout the cell body and processes. The portion of the capillary loop covered by mesangium (arrow) did not stain for PLA2R. In A and B, PLA2R was stained with a polyclonal anti-PLA2R antiserum generated in guinea pig, courtesy of G. Lambeau (Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, and Université de Nice-Sophia Antipolis, Valbonne, France). (C and D) PLA2R staining (green) of a MN kidney biopsy revealed a fine granular capillary loop pattern (C) nearly identical to that of IgG (D). PLA2R was stained with a commercial anti-PLA2R antibody generated in rabbit. (E) EM from a patient with primary MN showed electron-dense deposits (white asterisks) in a subepithelial position beneath the podocyte (P) and overlying the GBM. The podocyte exhibited condensation of the actin cytoskeleton and foot process effacement (arrows) and had laid down new ECM material (black asterisks) between the immune deposits. CL, capillary lumen. Original magnification, ×400 (A, C, and D), ×630 (B).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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Referenced in 3 patents
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