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Autoantibodies Targeting Nephrin in Podocytopathies

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Autoantibodies Targeting Nephrin in Podocytopathies. / Hengel, Felicitas E; Dehde, Silke; Lassé, Moritz; Zahner, Gunther; Seifert, Larissa; Schnarre, Annabel; Kretz, Oliver; Demir, Fatih; Pinnschmidt, Hans O; Grahammer, Florian; Lucas, Renke; Mehner, Lea Maxima; Zimmermann, Tom; Billing, Anja M; Oh, Jun; Mitrotti, Adele; Pontrelli, Paola; Debiec, Hanna; Dossier, Claire; Colucci, Manuela; Emma, Francesco; Smoyer, William E; Weins, Astrid; Schaefer, Franz; Alachkar, Nada; Diemert, Anke; Hogan, Julien; Hoxha, Elion; Wiech, Thorsten; Rinschen, Markus M; Ronco, Pierre; Vivarelli, Marina; Gesualdo, Loreto; Tomas, Nicola M; Huber, Tobias B; International Society of Glomerular Disease.

In: NEW ENGL J MED, Vol. 391, No. 5, 01.08.2024, p. 422-433.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Hengel, FE, Dehde, S, Lassé, M, Zahner, G, Seifert, L, Schnarre, A, Kretz, O, Demir, F, Pinnschmidt, HO, Grahammer, F, Lucas, R, Mehner, LM, Zimmermann, T, Billing, AM, Oh, J, Mitrotti, A, Pontrelli, P, Debiec, H, Dossier, C, Colucci, M, Emma, F, Smoyer, WE, Weins, A, Schaefer, F, Alachkar, N, Diemert, A, Hogan, J, Hoxha, E, Wiech, T, Rinschen, MM, Ronco, P, Vivarelli, M, Gesualdo, L, Tomas, NM, Huber, TB & International Society of Glomerular Disease 2024, 'Autoantibodies Targeting Nephrin in Podocytopathies', NEW ENGL J MED, vol. 391, no. 5, pp. 422-433. https://doi.org/10.1056/NEJMoa2314471

APA

Hengel, F. E., Dehde, S., Lassé, M., Zahner, G., Seifert, L., Schnarre, A., Kretz, O., Demir, F., Pinnschmidt, H. O., Grahammer, F., Lucas, R., Mehner, L. M., Zimmermann, T., Billing, A. M., Oh, J., Mitrotti, A., Pontrelli, P., Debiec, H., Dossier, C., ... International Society of Glomerular Disease (2024). Autoantibodies Targeting Nephrin in Podocytopathies. NEW ENGL J MED, 391(5), 422-433. https://doi.org/10.1056/NEJMoa2314471

Vancouver

Hengel FE, Dehde S, Lassé M, Zahner G, Seifert L, Schnarre A et al. Autoantibodies Targeting Nephrin in Podocytopathies. NEW ENGL J MED. 2024 Aug 1;391(5):422-433. https://doi.org/10.1056/NEJMoa2314471

Bibtex

@article{6e521e9af64445b8a8edd1e7ee90d3b7,
title = "Autoantibodies Targeting Nephrin in Podocytopathies",
abstract = "BACKGROUND: Minimal change disease and primary focal segmental glomerulosclerosis in adults, along with idiopathic nephrotic syndrome in children, are immune-mediated podocytopathies that lead to nephrotic syndrome. Autoantibodies targeting nephrin have been found in patients with minimal change disease, but their clinical and pathophysiological roles are unclear.METHODS: We conducted a multicenter study to analyze antinephrin autoantibodies in adults with glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, IgA nephropathy, antineutrophil cytoplasmic antibody-associated glomerulonephritis, and lupus nephritis, as well as in children with idiopathic nephrotic syndrome and in controls. We also created an experimental mouse model through active immunization with recombinant murine nephrin.RESULTS: The study included 539 patients (357 adults and 182 children) and 117 controls. Among the adults, antinephrin autoantibodies were found in 46 of the 105 patients (44%) with minimal change disease, 7 of 74 (9%) with primary focal segmental glomerulosclerosis, and only in rare cases among the patients with other conditions. Of the 182 children with idiopathic nephrotic syndrome, 94 (52%) had detectable antinephrin autoantibodies. In the subgroup of patients with active minimal change disease or idiopathic nephrotic syndrome who were not receiving immunosuppressive treatment, the prevalence of antinephrin autoantibodies was as high as 69% and 90%, respectively. At study inclusion and during follow-up, antinephrin autoantibody levels were correlated with disease activity. Experimental immunization induced a nephrotic syndrome, a minimal change disease-like phenotype, IgG localization to the podocyte slit diaphragm, nephrin phosphorylation, and severe cytoskeletal changes in mice.CONCLUSIONS: In this study, circulating antinephrin autoantibodies were common in patients with minimal change disease or idiopathic nephrotic syndrome and appeared to be markers of disease activity. Their binding at the slit diaphragm induced podocyte dysfunction and nephrotic syndrome, which highlights their pathophysiological significance. (Funded by Deutsche Forschungsgemeinschaft and others.).",
author = "Hengel, {Felicitas E} and Silke Dehde and Moritz Lass{\'e} and Gunther Zahner and Larissa Seifert and Annabel Schnarre and Oliver Kretz and Fatih Demir and Pinnschmidt, {Hans O} and Florian Grahammer and Renke Lucas and Mehner, {Lea Maxima} and Tom Zimmermann and Billing, {Anja M} and Jun Oh and Adele Mitrotti and Paola Pontrelli and Hanna Debiec and Claire Dossier and Manuela Colucci and Francesco Emma and Smoyer, {William E} and Astrid Weins and Franz Schaefer and Nada Alachkar and Anke Diemert and Julien Hogan and Elion Hoxha and Thorsten Wiech and Rinschen, {Markus M} and Pierre Ronco and Marina Vivarelli and Loreto Gesualdo and Tomas, {Nicola M} and Huber, {Tobias B} and {International Society of Glomerular Disease}",
note = "Copyright {\textcopyright} 2024 Massachusetts Medical Society.",
year = "2024",
month = aug,
day = "1",
doi = "10.1056/NEJMoa2314471",
language = "English",
volume = "391",
pages = "422--433",
journal = "NEW ENGL J MED",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "5",

}

RIS

TY - JOUR

T1 - Autoantibodies Targeting Nephrin in Podocytopathies

AU - Hengel, Felicitas E

AU - Dehde, Silke

AU - Lassé, Moritz

AU - Zahner, Gunther

AU - Seifert, Larissa

AU - Schnarre, Annabel

AU - Kretz, Oliver

AU - Demir, Fatih

AU - Pinnschmidt, Hans O

AU - Grahammer, Florian

AU - Lucas, Renke

AU - Mehner, Lea Maxima

AU - Zimmermann, Tom

AU - Billing, Anja M

AU - Oh, Jun

AU - Mitrotti, Adele

AU - Pontrelli, Paola

AU - Debiec, Hanna

AU - Dossier, Claire

AU - Colucci, Manuela

AU - Emma, Francesco

AU - Smoyer, William E

AU - Weins, Astrid

AU - Schaefer, Franz

AU - Alachkar, Nada

AU - Diemert, Anke

AU - Hogan, Julien

AU - Hoxha, Elion

AU - Wiech, Thorsten

AU - Rinschen, Markus M

AU - Ronco, Pierre

AU - Vivarelli, Marina

AU - Gesualdo, Loreto

AU - Tomas, Nicola M

AU - Huber, Tobias B

AU - International Society of Glomerular Disease

N1 - Copyright © 2024 Massachusetts Medical Society.

PY - 2024/8/1

Y1 - 2024/8/1

N2 - BACKGROUND: Minimal change disease and primary focal segmental glomerulosclerosis in adults, along with idiopathic nephrotic syndrome in children, are immune-mediated podocytopathies that lead to nephrotic syndrome. Autoantibodies targeting nephrin have been found in patients with minimal change disease, but their clinical and pathophysiological roles are unclear.METHODS: We conducted a multicenter study to analyze antinephrin autoantibodies in adults with glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, IgA nephropathy, antineutrophil cytoplasmic antibody-associated glomerulonephritis, and lupus nephritis, as well as in children with idiopathic nephrotic syndrome and in controls. We also created an experimental mouse model through active immunization with recombinant murine nephrin.RESULTS: The study included 539 patients (357 adults and 182 children) and 117 controls. Among the adults, antinephrin autoantibodies were found in 46 of the 105 patients (44%) with minimal change disease, 7 of 74 (9%) with primary focal segmental glomerulosclerosis, and only in rare cases among the patients with other conditions. Of the 182 children with idiopathic nephrotic syndrome, 94 (52%) had detectable antinephrin autoantibodies. In the subgroup of patients with active minimal change disease or idiopathic nephrotic syndrome who were not receiving immunosuppressive treatment, the prevalence of antinephrin autoantibodies was as high as 69% and 90%, respectively. At study inclusion and during follow-up, antinephrin autoantibody levels were correlated with disease activity. Experimental immunization induced a nephrotic syndrome, a minimal change disease-like phenotype, IgG localization to the podocyte slit diaphragm, nephrin phosphorylation, and severe cytoskeletal changes in mice.CONCLUSIONS: In this study, circulating antinephrin autoantibodies were common in patients with minimal change disease or idiopathic nephrotic syndrome and appeared to be markers of disease activity. Their binding at the slit diaphragm induced podocyte dysfunction and nephrotic syndrome, which highlights their pathophysiological significance. (Funded by Deutsche Forschungsgemeinschaft and others.).

AB - BACKGROUND: Minimal change disease and primary focal segmental glomerulosclerosis in adults, along with idiopathic nephrotic syndrome in children, are immune-mediated podocytopathies that lead to nephrotic syndrome. Autoantibodies targeting nephrin have been found in patients with minimal change disease, but their clinical and pathophysiological roles are unclear.METHODS: We conducted a multicenter study to analyze antinephrin autoantibodies in adults with glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, IgA nephropathy, antineutrophil cytoplasmic antibody-associated glomerulonephritis, and lupus nephritis, as well as in children with idiopathic nephrotic syndrome and in controls. We also created an experimental mouse model through active immunization with recombinant murine nephrin.RESULTS: The study included 539 patients (357 adults and 182 children) and 117 controls. Among the adults, antinephrin autoantibodies were found in 46 of the 105 patients (44%) with minimal change disease, 7 of 74 (9%) with primary focal segmental glomerulosclerosis, and only in rare cases among the patients with other conditions. Of the 182 children with idiopathic nephrotic syndrome, 94 (52%) had detectable antinephrin autoantibodies. In the subgroup of patients with active minimal change disease or idiopathic nephrotic syndrome who were not receiving immunosuppressive treatment, the prevalence of antinephrin autoantibodies was as high as 69% and 90%, respectively. At study inclusion and during follow-up, antinephrin autoantibody levels were correlated with disease activity. Experimental immunization induced a nephrotic syndrome, a minimal change disease-like phenotype, IgG localization to the podocyte slit diaphragm, nephrin phosphorylation, and severe cytoskeletal changes in mice.CONCLUSIONS: In this study, circulating antinephrin autoantibodies were common in patients with minimal change disease or idiopathic nephrotic syndrome and appeared to be markers of disease activity. Their binding at the slit diaphragm induced podocyte dysfunction and nephrotic syndrome, which highlights their pathophysiological significance. (Funded by Deutsche Forschungsgemeinschaft and others.).

U2 - 10.1056/NEJMoa2314471

DO - 10.1056/NEJMoa2314471

M3 - SCORING: Journal article

C2 - 38804512

VL - 391

SP - 422

EP - 433

JO - NEW ENGL J MED

JF - NEW ENGL J MED

SN - 0028-4793

IS - 5

ER -