title: Membranous Nephropathy Associated With Immunological Disorder-Related Liver Disease: A Retrospective Study of 10 Cases.
abstract: The association between membranous nephropathy (MN) and immunological disorder-related liver disease has not been extensively investigated, and the specific features of this uncommon association, if any, remain to be determined.We retrospectively identified 10 patients with this association. We aimed to describe the clinical, biological, and pathological characteristics of these patients and their therapeutic management. The possible involvement of the phospholipase A2 receptor (PLA2R) in these apparent secondary forms of MN was assessed by immunohistochemistry with renal and liver biopsy specimens.The mean delay between MN and liver disease diagnoses was 3.9 years and the interval between the diagnosis of the glomerular and liver diseases was <1.5 years in 5 patients. MN was associated with a broad spectrum of liver diseases including primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). AIH whether isolated (n = 3) or associated with PBC (n = 2) or PSC (n = 2) was the most frequent autoimmune liver disease. Circulating PLA2R antibodies were detected in 4 out of 9 patients but the test was performed under specific immunosuppressive treatment in 3 out of 9 patients. Seven of the 9 patients with available renal tissue specimens displayed enhanced expression of PLA2R in glomeruli whereas PLA2R was not expressed in liver parenchyma from these patients or in normal liver tissue. The study of immunoglobulin (Ig) subclasses of deposits in glomeruli revealed that the most frequent pattern was the coexistence of IgG1 and IgG4 immune deposits with IgG4 predominating.Detection of PLA2R antibodies in glomeruli but not in liver parenchyma is a common finding in patients with MN associated with autoimmune liver disease, suggesting that these autoantibodies are not exclusively detected in idiopathic MN.
authors.affiliation: From the Service de Néphrologie et Transplantation (MD, TK, TS, PR, PG, PL, DS, VA), Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Centre de référence maladie rare Syndrome Néphrotique Idiopathique, Institut Francilien de recherche en Néphrologie et Transplantation (IFRNT), DHU VIC (Virus-Immunité-Cancer), AP-HP (Assistance Publique-Hôpitaux de Paris), Université Paris Est Créteil (UPEC), Créteil, France; Equipe 21 (MD, AM, TK, TS, DD, PG, PL, DS, VA), INSERM Unité 955, Université Paris Est Créteil, Créteil, France; Département de Pathologie (AM, DD), Groupe Hospitalier Henri-Mondor/Albert-Chenevier, AP-HP, UPEC, Créteil, France; Service d'Anatomie pathologique (MR), Hôpital Necker - Enfants Malades, AP-HP, Université Paris Descartes, Paris, France; CHU Pontchaillou (CV, TF), Service de Néphrologie, Université de Rennes, Rennes, France; Service de Néphrologie et de Transplantation Rénale (SB), Hôpital de la Conception, AP-HM, Aix-Marseille Université, Marseille, France; Centre de Référence Maladies Rares des Maladies Inflammatoires des Voies Biliaires & Service d'Hépatologie (CC, OC), Hôpital Saint-Antoine, Centre de Référence Maladies Rares des Maladies Inflammatoires des Voies Biliaires & Service d'Hépatologie; Inserm, UMR-S 938, Centre de Recherche Saint-Antoine; AP-HP, Sorbonne Universités, Université Pierre et Marie Curie (UPMC), Paris, France; CHU Pontchaillou (N R-L), Service d'Anatomie Pathologie, Université de Rennes, Rennes, France; Service d'Anatomie pathologique (PR), Hôpital de la Pitié-Salpétrière, AP-HP, UPMC, Paris, France; Service de Néphrologie et Dialyse (BK), Hôpital Necker-Enfants Malades, AP-HP, Université Paris Descartes, Paris, France; Service de Néphrologie et Dialyses (J-J B, KD), Hôpital Tenon, AP-HP, UMPC, Paris, France; Service de Néphrologie (ED, MJ), Groupe hospitalier Bichat/Claude-Bernard, AP-HP, Université Paris Diderot, Paris, France; Service d'Anatomie pathologique (IB), Hôpital Tenon, AP-HP, UPMC, Paris, France.
authors.forename: Maxime
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authors.lastname: Dauvergne
authors.forename: Anissa
authors.initials: A
authors.lastname: Moktefi
authors.forename: Marion
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authors.lastname: Rabant
authors.forename: Cécile
authors.initials: C
authors.lastname: Vigneau
authors.forename: Tomek
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authors.lastname: Kofman
authors.forename: Stephane
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authors.lastname: Burtey
authors.forename: Christophe
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authors.lastname: Corpechot
authors.forename: Thomas
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authors.lastname: Stehlé
authors.forename: Dominique
authors.initials: D
authors.lastname: Desvaux
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rioux-Leclercq
authors.forename: Philippe
authors.initials: P
authors.lastname: Rouvier
authors.forename: Bertrand
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authors.lastname: Knebelmann
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Boffa
authors.forename: Thierry
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authors.lastname: Frouget
authors.forename: Eric
authors.initials: E
authors.lastname: Daugas
authors.forename: Mathieu
authors.initials: M
authors.lastname: Jablonski
authors.forename: Karine
authors.initials: K
authors.lastname: Dahan
authors.forename: Isabelle
authors.initials: I
authors.lastname: Brocheriou
authors.forename: Philippe
authors.initials: P
authors.lastname: Remy
authors.forename: Philippe
authors.initials: P
authors.lastname: Grimbert
authors.forename: Philippe
authors.initials: P
authors.lastname: Lang
authors.forename: Oliver
authors.initials: O
authors.lastname: Chazouilleres
authors.forename: Dil
authors.initials: D
authors.lastname: Sahali
authors.forename: Vincent
authors.initials: V
authors.lastname: Audard
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000150:complications* / Q000175:diagnosis / Q000276:immunology; D001706:Biopsy; D015209:Cholangitis, Sclerosing / Q000150:complications* / Q000175:diagnosis / Q000276:immunology; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D001323:Autoantibodies