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Review
. 2023 Dec 11;17(1):sfad228.
doi: 10.1093/ckj/sfad228. eCollection 2024 Jan.

Novel biomarkers and pathophysiology of membranous nephropathy: PLA2R and beyond

Corrado Murtas  1 , Maurizio Bruschi  2   3 , Sonia Spinelli  3 , Xhuliana Kajana  3 , Enrico E Verrina  3 , Andrea Angeletti  3 , Gianluca Caridi  3 , Giovanni Candiano  3 , Sandro Feriozzi  1 , Marco Prunotto  4 , Gian Marco Ghiggeri  3
Affiliations
Review

Novel biomarkers and pathophysiology of membranous nephropathy: PLA2R and beyond

Corrado Murtas et al. Clin Kidney J. .

Abstract

Research on membranous nephropathy truly exploded in the last 15 years. This happened because of the application of new techniques (laser capture microdissection, mass spectrometry, protein G immunoprecipitation, arrays) to the study of its pathogenesis. After the discovery of PLA2R as the major target antigen, many other antigens were identified and others are probably ongoing. Clinical and pathophysiology rebounds of new discoveries are relevant in terms of diagnosis and prognosis and it is time to make a first assessment of the innovative issues. In terms of classification, target antigens can be divided into: 'membrane antigens' and 'second wave' antigens. The first group consists of antigens constitutionally expressed on the podocyte membrane (as PLA2R) that may become a target of an autoimmune process because of perturbation of immune-tolerance. 'Second wave' antigens are antigens neo-expressed by the podocyte or by infiltrating cells after a stressing event: this allows the immune system to produce antibodies against them that intensify and maintain glomerular damage. With this abundance of target antigens it is not possible, at the moment, to test all antibodies at the bedside. In the absence of this possibility, the role of histological evaluation is still irreplaceable.

Keywords: glomerulonephritis; membranous nephropathy; oxidative systems; phospholipase-A2; superoxide dismutase.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1:
Figure 1:
Scheme reproducing the possible steps of MN and the interactive nature of first and second autoimmune hits.
Figure 2:
Figure 2:
Stainings of a renal bioptic fragment from a patient with MN with anti-CDl8 and anti-FMNL1 antibodies immunoperoxidase staining.
See this image and copyright information in PMC

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