title: Genetic homogeneity but IgG subclass-dependent clinical variability of alloimmune membranous nephropathy with anti-neutral endopeptidase antibodies.
abstract: Alloimmune antenatal membranous nephropathy (MN) during pregnancy results from antibodies produced by a neutral endopeptidase (NEP)-deficient mother. Here we report two recent cases that provide clues to the severity of renal disease. Mothers of the two children had circulating antibodies against NEP showing the characteristic species-dependent pattern by immunofluorescence on kidney slices. A German mother produced predominantly anti-NEP IgG4 accompanied by a low amount of IgG1. Her child recovered renal function within a few weeks. In sharp contrast, an Italian mother mainly produced complement-fixing anti-NEP IgG1, which also inhibits NEP enzymatic activity, whereas anti-NEP IgG4 has a weak inhibitory potency. Her child was dialyzed for several weeks. A kidney biopsy performed at 12 days of age showed MN, ischemic glomeruli, and arteriolar and tubular lesions. A second biopsy performed at 12 weeks of age showed aggravation with an increased number of collapsed capillary tufts. Both mothers were homozygous for the truncating deletion mutation 466delC and were thus NEP deficient. The 466delC mutation, identified in three previously described families, suggests a founder effect. Because of the potential severity of alloimmune antenatal MN, it is essential to identify families at risk by the detection of anti-NEP antibodies and NEP antigen in urine. On the basis of the five families identified to date, we propose an algorithm for the diagnosis of the disease and the prevention of complications.
authors.affiliation: Division of Nephrology and Dialysis, Children's Hospital Bambino Gesù, IRCCS, Rome, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Vivarelli
authors.affiliation: Division of Nephrology and Dialysis, Children's Hospital Bambino Gesù, IRCCS, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Emma
authors.affiliation: 1] Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1155, Paris, France [2] INSERM, UMR_S 1155, Hôpital Tenon, Paris, France.
authors.forename: Thimothée
authors.initials: T
authors.lastname: Pellé
authors.affiliation: Department of Pediatrics, Philipps University, Marburg, Marburg, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Gerken
authors.affiliation: 8216;Rina Balducci' Center of Pediatric Endocrinology, Tor Vergata University, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Pedicelli
authors.affiliation: Department of Laboratories-Pathology Unit, Children's Hospital Bambino Gesù, IRCCS, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Diomedi-Camassei
authors.affiliation: Department of Pediatrics, Philipps University, Marburg, Marburg, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Klaus
authors.affiliation: Department of Pediatrics, Philipps University, Marburg, Marburg, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Waldegger
authors.affiliation: 1] Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1155, Paris, France [2] INSERM, UMR_S 1155, Hôpital Tenon, Paris, France [3] Department of Nephrology and Dialysis, AP-HP, Hôpital Tenon, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Ronco
authors.affiliation: 1] Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1155, Paris, France [2] INSERM, UMR_S 1155, Hôpital Tenon, Paris, France.
authors.forename: Hanna
authors.initials: H
authors.lastname: Debiec
mesh_terms: D005260:Female; D005315:Fetal Diseases / Q000235:genetics / Q000276:immunology*; D015433:Glomerulonephritis, Membranous / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D006720:Homozygote; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification*; D007231:Infant, Newborn; D007234:Infant, Premature; D015260:Neprilysin / Q000235:genetics / Q000276:immunology*; D011247:Pregnancy; D006435:Renal Dialysis
chemical_list: D007074:Immunoglobulin G; D015260:Neprilysin