Last update:

   09-Sep-2020
 

Arch Hellen Med, 37(Supplement 2), 2020, 125-128

LABORATORY PROCEDURE

The hard way from bench to bedside History lessons
from the pathogenesis of idiopathic membranous nephropathy (MN)

I. Stefanidis,1 E. Nikolaou,1 F. Karasavvidou,2 T. Eleftheriadis,1 A. Diamandopoulos3
1Department of Nephrology, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa
2Laboratory of Pharmacology, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa
3Medical School, National and Kapodistrian University of Athens, Athens, and Louros Foundation for the History of Medicine, Athens, Greece

Membranous nephropathy (MN) is one of the most common causes of adult nephrotic syndrome. Histopathology involves typical subepithelial immuncomplexes, with an obvious pathogenetic role. Today, the study of pathogenesis, which began in 1959, has proven that MN is an organ-specific autoimmune disease. Our aim was to follow and draw some historical lessons from this 60-year long course of studies on MN. Heymann nephritis (HN; 1959) is the classical animal model, in which the pathogenetic role of immuncomplexes in MN was first established. HN is induced by injection in rats of tubules brush border (BB) antigens (active HN) or the corresponding antibodies (anti-BB; passive HN). In 1978, lesions of HN forming ex vivo after anti-BB injection in an isolated perfused rat kidney model, i.e. in the absence of circulating BB antigens, proved that immune-complex formation occurs in situ. In 1982, megalin was identified as the epithelial auto-antigen in HN. However, as megalin could not be detected in human podocytes, pathogenesis of human MN still remained unresolved. In 2002, neutral endopeptidase was identified as the podocyte antigen in cases of antenatal allo-immune human MN, clearly implicating the pathogenetic role of podocyte membrane proteins and in situ immune-complex formation. In the next years, phospholipase A2-receptor and Thrombospondin type-1 domain containing 7A were identified as organ-specific auto-antigens associated with MN. The maxim "sciencia facit altus" could precisely describe the evolution of 60 years of research on the pathogenesis of MN, which was decisively promoted with the breakthroughs made in the last 20 years. This pattern may change as we reach the exciting new scientific era.

Key words: Heymann nephritis, History of medical research procedures, Megalin, Membranous nephropathy.


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