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Nephrol Ther. 2017 Apr;13 Suppl 1:S75-S81. doi: 10.1016/j.nephro.2017.01.012.

[Membranous nephropathy: Pathophysiology and natural history].

[Article in French]

Author information

1
Laboratoire d'immunologie, hôpital l'Archet, CHU de Nice, université de Nice-Sophia Antipolis, 06202 Nice cedex 3, France; UMR 7275, institut de pharmacologie moléculaire et cellulaire, CNRS, Sophia Antipolis, 660, route des Lucioles, 06560 Valbonne, France; Service de néphrologie, hôpital Pasteur, université de Nice-Sophia Antipolis, CHU de Nice, 30, voie romaine, CS 51069, 06001 Nice cedex 1, France. Electronic address: seitz-polski.b@chu-nice.fr.
2
UMR 7275, institut de pharmacologie moléculaire et cellulaire, CNRS, Sophia Antipolis, 660, route des Lucioles, 06560 Valbonne, France.
3
Service de néphrologie, hôpital Pasteur, université de Nice-Sophia Antipolis, CHU de Nice, 30, voie romaine, CS 51069, 06001 Nice cedex 1, France.

Abstract

Membranous nephropathy is a major cause of nephrotic syndrome in adults, with various etiologies and outcomes. One third of patients enter spontaneous remission with blockade of the renin-angiotensin system, one third develop a persistent nephrotic syndrome, while another third of patients develop end-stage kidney disease and 40% of them relapse after kidney transplantation. Treatment of membranous nephropathy remains controversial. Immunosuppressive therapy is only recommended in case of renal function deterioration or persistent nephrotic syndrome after 6months of renin-angiotensin system blockade. Therefore, delayed immunosuppressive treatments may lead to significant and potentially irreversible complications. For long, no biological markers could predict clinical outcome and guide therapy. The discovery of autoantibodies to the phospholipase A2 receptor (PLA2R1) in 2009, and to the thrombospondin type 1 domain containing 7A (THSD7A) in 2014 in respectively 70 and 5% of patients with membranous nephropathy were major breakthroughs. The passive infusion of human anti-THSD7A antibodies in mouse induces proteinuria and membranous nephropathy. The identification of these antigens has allowed developing diagnostic and prognostic tests. High anti-PLA2R1 titers at time of diagnosis predict a poor renal outcome. Anti-PLA2R1 antibodies can bind at least three different domains of PLA2R1. Epitope spreading with binding of two or three of these antigenic domains is associated with active membranous nephropathy and poor renal survival. These new tools could help us to monitor disease severity and to predict renal prognosis for a better selection of patients that should benefit of early immunosuppressive therapy.

KEYWORDS:

Anti-PLA2R1 antibodies; Anticorps anti-PLA2R1; Epitope spreading; Glomérulonéphrite extramembraneuse; Membranous nephropathy; Étalement d’épitopes

PMID:
28577747
DOI:
10.1016/j.nephro.2017.01.012
[Indexed for MEDLINE]

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