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Article ; Online: When contactin antibodies hit the podocyte: a new neurorenal syndrome.

Debiec, Hanna / Ronco, Pierre

2021 Volume 100, Issue 6, Page(s) 1163–1165

Abstract: Membranous nephropathy can be associated with various etiologies and antigens. In this issue of Kidney International, Le Quintrec et al. described contactin-1 cell adhesion molecule as a novel target antigen shared by the peripheral nerve and podocyte in ...

Abstract	Membranous nephropathy can be associated with various etiologies and antigens. In this issue of Kidney International, Le Quintrec et al. described contactin-1 cell adhesion molecule as a novel target antigen shared by the peripheral nerve and podocyte in patients with neurological disease and membranous nephropathy.
MeSH term(s)	Antibodies ; Contactins ; Glomerulonephritis, Membranous/drug therapy ; Humans ; Kidney ; Podocytes
Chemical Substances	Antibodies ; Contactins
Language	English
Publishing date	2021-11-21
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2021.09.022
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Article ; Online: Membranous nephropathy: current understanding of various causes in light of new target antigens.

Ronco, Pierre / Debiec, Hanna

Current opinion in nephrology and hypertension

2021 Volume 30, Issue 3, Page(s) 287–293

Abstract: Purpose of review: Membranous nephropathy is an autoimmune disease caused by antibodies mostly directed to podocyte antigens. PLA2R and THSD7A antigens were described in 2009 and 2014 using classical immunochemical techniques. In the last 2 years, ... ...

Abstract	Purpose of review: Membranous nephropathy is an autoimmune disease caused by antibodies mostly directed to podocyte antigens. PLA2R and THSD7A antigens were described in 2009 and 2014 using classical immunochemical techniques. In the last 2 years, thanks to the combination of laser microdissection of glomeruli and mass spectrometry of solubilized digested proteins, several antigens associated with various causes have been described in patients with membranous nephropathy. The purpose of this review is to report on those "new" antigens and to analyse the clinicopathological correlations that make each of this antigen unique. Recent findings: This article covers the literature of the last 2 years devoted to the description of those new antigens and biomarkers including NELL-1 and Semaphorin 3B in primary membranous nephropathy, and exostosins 1 and 2 and NCAM in lupus class V membranous nephropathy, which will be compared with the previously described antigens. These findings will lead to propose a new classification of membranous nephropathy based on serology and tissue antigen identification that could/should substitute for the classical distinction between primary and secondary membranous nephropathy. Summary: The discovery of the latest antigens has major implications for the care of patients with membranous nephropathy as they drive the etiologic investigations and provide invaluable markers for treatment monitoring.
MeSH term(s)	Antigens ; Glomerulonephritis, Membranous/diagnosis ; Glomerulonephritis, Membranous/immunology ; Humans ; Podocytes/immunology ; Podocytes/pathology
Chemical Substances	Antigens
Language	English
Publishing date	2021-01-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1151092-4
ISSN	1473-6543 ; 1535-3842 ; 1062-4813 ; 1062-4821
ISSN (online)	1473-6543 ; 1535-3842
ISSN	1062-4813 ; 1062-4821
DOI	10.1097/MNH.0000000000000697
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Zs.A 3686: Show issues

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Article ; Online: A child with semaphorin 3b-associated membranous nephropathy effectively treated with obinutuzumab after rituximab resistance.

Conversano, Ester / Debiec, Hanna / Colucci, Manuela / Emma, Francesco / Ronco, Pierre / Vivarelli, Marina

Pediatric nephrology (Berlin, Germany)

2023 Volume 39, Issue 1, Page(s) 305–308

Abstract: Background: Membranous nephropathy is a glomerular disease characterized by the presence of immune-complexes deposited in the subepithelial space of the glomerular basement membrane. It is the main cause of nephrotic syndrome in adults, while in ... ...

Abstract	Background: Membranous nephropathy is a glomerular disease characterized by the presence of immune-complexes deposited in the subepithelial space of the glomerular basement membrane. It is the main cause of nephrotic syndrome in adults, while in children it is very infrequent. Anti-CD20 monoclonal antibodies, mainly rituximab, represent a specific treatment for this disease. Case report: We report the case of a child presenting at 2 years of age with steroid-resistant nephrotic syndrome diagnosed upon kidney biopsy as semaphorin 3B (SEMA3B)-associated primary membranous nephropathy. The patient responded to treatment with cyclosporine, but invariably relapsed upon tapering of this agent. Therefore, at age 9, he was successfully treated with rituximab to overcome cyclosporine dependence. However, after the second rituximab infusion, a rapid reconstitution of CD19 + B cells and a relapse of proteinuria occurred, requiring reintroduction of cyclosporine. Obinutuzumab, a type II anti-CD20 monoclonal antibody, was then infused inducing prolonged CD19 + B cell depletion and remission of proteinuria despite discontinuation of cyclosporine. A greater reduction in circulating anti-SEMA3B antibodies assessed by Western blot was observed after obinutuzumab compared with rituximab infusion. Discussion: Obinutuzumab was safe and well-tolerated, and may therefore represent an effective therapeutic alternative in children with primary MN and rituximab resistance.
MeSH term(s)	Humans ; Male ; Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents/therapeutic use ; Cyclosporine/therapeutic use ; Glomerulonephritis, Membranous/pathology ; Nephrotic Syndrome/etiology ; Nephrotic Syndrome/complications ; Proteinuria/drug therapy ; Rituximab/therapeutic use ; Semaphorins/therapeutic use ; Child, Preschool
Chemical Substances	Antibodies, Monoclonal ; Antineoplastic Agents ; Cyclosporine (83HN0GTJ6D) ; obinutuzumab (O43472U9X8) ; Rituximab (4F4X42SYQ6) ; Semaphorins
Language	English
Publishing date	2023-07-19
Publishing country	Germany
Document type	Case Reports ; Journal Article
ZDB-ID	631932-4
ISSN	1432-198X ; 0931-041X
ISSN (online)	1432-198X
ISSN	0931-041X
DOI	10.1007/s00467-023-06085-8
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Zs.A 2196: Show issues

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Article ; Online: Molecular Pathogenesis of Membranous Nephropathy.

Ronco, Pierre / Debiec, Hanna

Annual review of pathology

2019 Volume 15, Page(s) 287–313

Abstract: Membranous nephropathy is a noninflammatory autoimmune disease of the kidney glomerulus, characterized by the formation of immune deposits, complement-mediated proteinuria, and risk of renal failure. Considerable advances in understanding the molecular ... ...

Abstract	Membranous nephropathy is a noninflammatory autoimmune disease of the kidney glomerulus, characterized by the formation of immune deposits, complement-mediated proteinuria, and risk of renal failure. Considerable advances in understanding the molecular pathogenesis have occurred with the identification of several antigens [neutral endopeptidase, phospholipase A2 receptor (PLA
MeSH term(s)	Adult ; Autoantibodies/blood ; Biomarkers/blood ; Disease Progression ; Genetic Predisposition to Disease ; Glomerulonephritis, Membranous/genetics ; Glomerulonephritis, Membranous/immunology ; Glomerulonephritis, Membranous/pathology ; HLA Antigens/genetics ; HLA Antigens/immunology ; Humans ; Infant, Newborn ; Neprilysin/immunology ; Neprilysin/metabolism ; Receptors, Phospholipase A2/immunology ; Receptors, Phospholipase A2/metabolism ; Risk Factors ; Thrombospondins/immunology ; Thrombospondins/metabolism
Chemical Substances	Autoantibodies ; Biomarkers ; HLA Antigens ; Receptors, Phospholipase A2 ; THSD7A protein, human ; Thrombospondins ; Neprilysin (EC 3.4.24.11)
Language	English
Publishing date	2019-10-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2227429-7
ISSN	1553-4014 ; 1553-4006
ISSN (online)	1553-4014
ISSN	1553-4006
DOI	10.1146/annurev-pathol-020117-043811
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Article ; Online: The role of PLA2R antibody monitoring: what we know and what we do not know.

Ronco, Pierre / Plaisier, Emmanuelle / Debiec, Hanna

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

2021 Volume 38, Issue 4, Page(s) 826–833

Abstract: For a long time, kidney biopsy was the only diagnostic means for membranous nephropathy (MN) and proteinuria and serum creatinine were the only markers of disease activity. The discovery of the phospholipase A2 receptor (PLA2R) antibody in 2009 has ... ...

Abstract	For a long time, kidney biopsy was the only diagnostic means for membranous nephropathy (MN) and proteinuria and serum creatinine were the only markers of disease activity. The discovery of the phospholipase A2 receptor (PLA2R) antibody in 2009 has induced a paradigm shift in both the diagnosis and monitoring of patients. Two serological tests are routinely used: the enzyme-linked immunosorbent assay (ELISA), which is quantitative, and the immunofluorescence assay (IFA), which is more sensitive. In centres where the two assays are available, the recommendation is to use IFA for screening and diagnosis of immunological remission and ELISA for monitoring the effectiveness of therapy. In patients with positive PLA2R antibody serology, normal kidney function and no evidence of an underlying disease, a kidney biopsy is not mandatory given the almost 100% specificity of the assays. Because MN has different phases, one cannot base a clinical or therapeutic decision on a single measurement of PLA2R antibody at baseline. Risk evaluation of disease progression is a dynamic process that should be performed repeatedly to capture the trajectory of the disease based on both the traditional biomarkers (proteinuria and serum creatinine) and PLA2R antibody levels. The effectiveness of therapy is also evaluated on the PLA2R antibody trajectory, particularly during the first 6 months. Finally, PLA2R antibody monitoring has transformed the management of patients with kidney allografts. Future studies are needed to develop more subtle immunological tests, including monitoring of antigen-specific memory B cells.
MeSH term(s)	Humans ; Receptors, Phospholipase A2 ; Creatinine ; Autoantibodies ; Kidney/pathology ; Glomerulonephritis, Membranous/pathology ; Proteinuria/pathology ; Biomarkers
Chemical Substances	Receptors, Phospholipase A2 ; Creatinine (AYI8EX34EU) ; Autoantibodies ; Biomarkers
Language	English
Publishing date	2021-12-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	90594-x
ISSN	1460-2385 ; 0931-0509
ISSN (online)	1460-2385
ISSN	0931-0509
DOI	10.1093/ndt/gfab356
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Zs.A 2198: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 329: Show issues

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Article: Advances in Membranous Nephropathy.

Ronco, Pierre / Plaisier, Emmanuelle / Debiec, Hanna

Journal of clinical medicine

2021 Volume 10, Issue 4

Abstract: Membranous nephropathy (MN) is a rare auto-immune disease where the glomerulus is targeted by circulating auto-antibodies mostly against podocyte antigens, which results in the formation of electron-dense immune complexes, activation of complement and ... ...

Abstract	Membranous nephropathy (MN) is a rare auto-immune disease where the glomerulus is targeted by circulating auto-antibodies mostly against podocyte antigens, which results in the formation of electron-dense immune complexes, activation of complement and massive proteinuria. MN is the most common cause of nephrotic syndrome in adults leading to severe thrombotic complications and kidney failure. This review is focused on the recent therapeutic and pathophysiological advances that occurred in the last two years. For a long time, we were lacking a head-to-head comparison between cyclophosphamide considered as the gold standard therapy and other medications, notably rituximab. Substantial progress has been achieved owing to three randomized controlled trials. MENTOR (Membranous Nephropathy Trial of Rituximab) and STARMEN (Sequential Therapy with Tacrolimus and Rituximab in Primary Membranous Nephropathy) conclusively established that calcineurin inhibitor-based regimens are slower to result in an immunologic response than rituximab or cyclophosphamide, achieve fewer complete clinical remissions, and are less likely to maintainremission. Rituximab Versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (RI-CYCLO) suggested that competition between cyclophosphamide and rituximab remains open. Given the technological leap combining laser microdissection of glomeruli and mass spectrometry of solubilized digested proteins, four "new antigens" were discovered including NELL-1 and Semaphorin 3B in so-called primary MN, and exostosins 1 and 2 and NCAM 1 in lupus MN. NELL-1 is associated with about 8% of primary MN and is characterized by segmental immune deposits and frequent association with cancer (30%). Semaphorin 3B-associated MN usually occurs in children, often below the age of two years, where it is the main antigen, representing about 16% of non-lupus MN in childhood. Exostosins 1/2 and NCAM 1 are associated with 30% and 6% of lupus MN, respectively. Exostosins 1/2 (EXT1/2) staining is associated with a low rate of end-stage kidney disease (ESKD) even in mixed classes III/IV+V. These findings already lead to revisiting the diagnostic and therapeutic algorithms toward more personalized medicine.
Language	English
Publishing date	2021-02-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm10040607
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Article ; Online: Cubilin and amnionless protein are novel target antigens in anti-brush border antibody disease.

Morelle, Johann / Caza, Tiffany / Debiec, Hanna / Aydin, Selda / Storey, Aaron / Ronco, Pierre / Larsen, Christopher

Kidney international

2022 Volume 101, Issue 5, Page(s) 1063–1068

MeSH term(s)	Kidney Tubules, Proximal/metabolism ; Receptors, Cell Surface/metabolism
Chemical Substances	Receptors, Cell Surface ; intrinsic factor-cobalamin receptor
Language	English
Publishing date	2022-03-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2022.02.021
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Article ; Online: Contactin-1-associated membranous nephropathy: complete immunologic and clinical remission with rituximab.

Plaisier, Emmanuelle / Not, Adeline / Buob, David / Ronco, Pierre / Debiec, Hanna

Kidney international

2021 Volume 100, Issue 6, Page(s) 1342–1344

MeSH term(s)	Contactin 1 ; Glomerulonephritis, Membranous/diagnosis ; Glomerulonephritis, Membranous/drug therapy ; Humans ; Immunologic Factors/therapeutic use ; Receptors, Phospholipase A2 ; Rituximab/therapeutic use
Chemical Substances	Contactin 1 ; Immunologic Factors ; Receptors, Phospholipase A2 ; Rituximab (4F4X42SYQ6)
Language	English
Publishing date	2021-11-21
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2021.08.029
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Article ; Online: Advances in Membranous Nephropathy

Pierre Ronco / Emmanuelle Plaisier / Hanna Debiec

Journal of Clinical Medicine, Vol 10, Iss 4, p

2021 Volume 607

Abstract	Membranous nephropathy (MN) is a rare auto-immune disease where the glomerulus is targeted by circulating auto-antibodies mostly against podocyte antigens, which results in the formation of electron-dense immune complexes, activation of complement and massive proteinuria. MN is the most common cause of nephrotic syndrome in adults leading to severe thrombotic complications and kidney failure. This review is focused on the recent therapeutic and pathophysiological advances that occurred in the last two years. For a long time, we were lacking a head-to-head comparison between cyclophosphamide considered as the gold standard therapy and other medications, notably rituximab. Substantial progress has been achieved owing to three randomized controlled trials. MENTOR (Membranous Nephropathy Trial of Rituximab) and STARMEN (Sequential Therapy with Tacrolimus and Rituximab in Primary Membranous Nephropathy) conclusively established that calcineurin inhibitor-based regimens are slower to result in an immunologic response than rituximab or cyclophosphamide, achieve fewer complete clinical remissions, and are less likely to maintainremission. Rituximab Versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (RI-CYCLO) suggested that competition between cyclophosphamide and rituximab remains open. Given the technological leap combining laser microdissection of glomeruli and mass spectrometry of solubilized digested proteins, four “new antigens” were discovered including NELL-1 and Semaphorin 3B in so-called primary MN, and exostosins 1 and 2 and NCAM 1 in lupus MN. NELL-1 is associated with about 8% of primary MN and is characterized by segmental immune deposits and frequent association with cancer (30%). Semaphorin 3B-associated MN usually occurs in children, often below the age of two years, where it is the main antigen, representing about 16% of non-lupus MN in childhood. Exostosins 1/2 and NCAM 1 are associated with 30% and 6% of lupus MN, respectively. Exostosins 1/2 (EXT1/2) staining ...
Keywords	membranous nephropathy ; randomized controlled trials ; rituximab ; KDIGO recommendations ; PLA2R ; THSD7A ; Medicine ; R
Subject code	610
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: A podocyte view of membranous nephropathy: from Heymann nephritis to the childhood human disease.

Ronco, Pierre / Debiec, Hanna

Pflugers Archiv : European journal of physiology

2017 Volume 469, Issue 7-8, Page(s) 997–1005

Abstract: Membranous nephropathy (MN) is characterized by an accumulation of immune deposits on the subepithelial side of the glomerular basement membrane, which results in complement activation and proteinuria. Since 2002, several major antigens of the podocyte ... ...

Abstract	Membranous nephropathy (MN) is characterized by an accumulation of immune deposits on the subepithelial side of the glomerular basement membrane, which results in complement activation and proteinuria. Since 2002, several major antigens of the podocyte have been identified in human MN, the first one being neutral endopeptidase (NEP), the alloantigen involved in neonatal cases of MN that occur in newborns from NEP-deficient mothers. This discovery opened the field to the major advances that have occurred since then in the pathophysiology and treatment of MN. It is remarkable that experimental models such as Heymann nephritis and cationic bovine serum albumin-induced MN in the rabbit predicted the pathomechanisms of the human glomerulopathy. The podocyte is at the center of the pathogenesis of MN either by providing a source of endogenous antigens or by creating an environment favorable to deposition and accumulation of immune complexes containing exogenous (non-podocyte) antigens. The podocyte is also a victim of complement activation and antibody blocking activity against enzymes or receptors. A search for innovative drugs aimed at protecting this cell against complement activation and the effects of prolonged ER stress has become a priority.
Language	English
Publishing date	2017-08
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	6380-0
ISSN	1432-2013 ; 0031-6768
ISSN (online)	1432-2013
ISSN	0031-6768
DOI	10.1007/s00424-017-2007-x
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