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Netrin G1 is a Novel Target Antigen in Primary Membranous Nephropathy

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Netrin G1 is a Novel Target Antigen in Primary Membranous Nephropathy. / Reinhard, Linda; Machalitza, Maya; Wiech, Thorsten; Groene, Hermann-Josef; Lassé, Moritz; Rinschen, Markus; Ferru, Nicoletta; Bräsen, Jan; Drömann, Friederike; Rob, Peter; Sethi, Sanjeev; Hoxha, Elion; Stahl, Rolf.

In: J AM SOC NEPHROL, Vol. 33, No. 10, 10.2022, p. 1823-1831.

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

Harvard

Reinhard, L, Machalitza, M, Wiech, T, Groene, H-J, Lassé, M, Rinschen, M, Ferru, N, Bräsen, J, Drömann, F, Rob, P, Sethi, S, Hoxha, E & Stahl, R 2022, 'Netrin G1 is a Novel Target Antigen in Primary Membranous Nephropathy', J AM SOC NEPHROL, vol. 33, no. 10, pp. 1823-1831. https://doi.org/10.1681/ASN.2022050608

APA

Reinhard, L., Machalitza, M., Wiech, T., Groene, H-J., Lassé, M., Rinschen, M., Ferru, N., Bräsen, J., Drömann, F., Rob, P., Sethi, S., Hoxha, E., & Stahl, R. (2022). Netrin G1 is a Novel Target Antigen in Primary Membranous Nephropathy. J AM SOC NEPHROL, 33(10), 1823-1831. https://doi.org/10.1681/ASN.2022050608

Vancouver

Reinhard L, Machalitza M, Wiech T, Groene H-J, Lassé M, Rinschen M et al. Netrin G1 is a Novel Target Antigen in Primary Membranous Nephropathy. J AM SOC NEPHROL. 2022 Oct;33(10):1823-1831. https://doi.org/10.1681/ASN.2022050608

Bibtex

@article{6c3f123e5c314029ba097f89a47b0160,
title = "Netrin G1 is a Novel Target Antigen in Primary Membranous Nephropathy",
abstract = "BACKGROUND: Primary membranous nephropathy (MN) is caused by circulating autoantibodies binding to antigens on the podocyte surface. PLA2R1 is the main target antigen in 70%-80% of cases, but the pathogenesis is unresolved in 10%-15% of patients.METHODS: We used native western blotting to identify IgG4 autoantibodies, which bind an antigen endogenously expressed on podocyte membranes, in the serum of the index patient with MN. These IgG4 autoantibodies were used to immunoprecipitate the target antigen, and mass spectrometry was used to identify Netrin G1 (NTNG1). Using native western blot and ELISA, NTNG1 autoantibodies were analyzed in cohorts of 888 patients with MN or other glomerular diseases.RESULTS: NTNG1 was identified as a novel target antigen in MN. It is a membrane protein expressed in healthy podocytes. Immunohistochemistry confirmed granular NTNG1 positivity in subepithelial glomerular immune deposits. In prospective and retrospective MN cohorts, we identified three patients with NTNG1-associated MN who showed IgG4-dominant circulating NTNG1 autoantibodies, enhanced NTNG1 expression in the kidney, and glomerular IgG4 deposits. No NTNG1 autoantibodies were identified in 561 PLA2R1 autoantibodies-positive patients, 27 THSD7A autoantibodies-positive patients, and 77 patients with other glomerular diseases. In two patients with available follow-up of 2 and 4 years, both NTNG1 autoantibodies and proteinuria persisted.CONCLUSIONS: NTNG1 expands the repertoire of target antigens in patients with MN. The clinical role of NTNG1 autoantibodies remains to be defined.",
author = "Linda Reinhard and Maya Machalitza and Thorsten Wiech and Hermann-Josef Groene and Moritz Lass{\'e} and Markus Rinschen and Nicoletta Ferru and Jan Br{\"a}sen and Friederike Dr{\"o}mann and Peter Rob and Sanjeev Sethi and Elion Hoxha and Rolf Stahl",
year = "2022",
month = oct,
doi = "10.1681/ASN.2022050608",
language = "English",
volume = "33",
pages = "1823--1831",
journal = "J AM SOC NEPHROL",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "10",

}

RIS

TY - JOUR

T1 - Netrin G1 is a Novel Target Antigen in Primary Membranous Nephropathy

AU - Reinhard, Linda

AU - Machalitza, Maya

AU - Wiech, Thorsten

AU - Groene, Hermann-Josef

AU - Lassé, Moritz

AU - Rinschen, Markus

AU - Ferru, Nicoletta

AU - Bräsen, Jan

AU - Drömann, Friederike

AU - Rob, Peter

AU - Sethi, Sanjeev

AU - Hoxha, Elion

AU - Stahl, Rolf

PY - 2022/10

Y1 - 2022/10

N2 - BACKGROUND: Primary membranous nephropathy (MN) is caused by circulating autoantibodies binding to antigens on the podocyte surface. PLA2R1 is the main target antigen in 70%-80% of cases, but the pathogenesis is unresolved in 10%-15% of patients.METHODS: We used native western blotting to identify IgG4 autoantibodies, which bind an antigen endogenously expressed on podocyte membranes, in the serum of the index patient with MN. These IgG4 autoantibodies were used to immunoprecipitate the target antigen, and mass spectrometry was used to identify Netrin G1 (NTNG1). Using native western blot and ELISA, NTNG1 autoantibodies were analyzed in cohorts of 888 patients with MN or other glomerular diseases.RESULTS: NTNG1 was identified as a novel target antigen in MN. It is a membrane protein expressed in healthy podocytes. Immunohistochemistry confirmed granular NTNG1 positivity in subepithelial glomerular immune deposits. In prospective and retrospective MN cohorts, we identified three patients with NTNG1-associated MN who showed IgG4-dominant circulating NTNG1 autoantibodies, enhanced NTNG1 expression in the kidney, and glomerular IgG4 deposits. No NTNG1 autoantibodies were identified in 561 PLA2R1 autoantibodies-positive patients, 27 THSD7A autoantibodies-positive patients, and 77 patients with other glomerular diseases. In two patients with available follow-up of 2 and 4 years, both NTNG1 autoantibodies and proteinuria persisted.CONCLUSIONS: NTNG1 expands the repertoire of target antigens in patients with MN. The clinical role of NTNG1 autoantibodies remains to be defined.

AB - BACKGROUND: Primary membranous nephropathy (MN) is caused by circulating autoantibodies binding to antigens on the podocyte surface. PLA2R1 is the main target antigen in 70%-80% of cases, but the pathogenesis is unresolved in 10%-15% of patients.METHODS: We used native western blotting to identify IgG4 autoantibodies, which bind an antigen endogenously expressed on podocyte membranes, in the serum of the index patient with MN. These IgG4 autoantibodies were used to immunoprecipitate the target antigen, and mass spectrometry was used to identify Netrin G1 (NTNG1). Using native western blot and ELISA, NTNG1 autoantibodies were analyzed in cohorts of 888 patients with MN or other glomerular diseases.RESULTS: NTNG1 was identified as a novel target antigen in MN. It is a membrane protein expressed in healthy podocytes. Immunohistochemistry confirmed granular NTNG1 positivity in subepithelial glomerular immune deposits. In prospective and retrospective MN cohorts, we identified three patients with NTNG1-associated MN who showed IgG4-dominant circulating NTNG1 autoantibodies, enhanced NTNG1 expression in the kidney, and glomerular IgG4 deposits. No NTNG1 autoantibodies were identified in 561 PLA2R1 autoantibodies-positive patients, 27 THSD7A autoantibodies-positive patients, and 77 patients with other glomerular diseases. In two patients with available follow-up of 2 and 4 years, both NTNG1 autoantibodies and proteinuria persisted.CONCLUSIONS: NTNG1 expands the repertoire of target antigens in patients with MN. The clinical role of NTNG1 autoantibodies remains to be defined.

U2 - 10.1681/ASN.2022050608

DO - 10.1681/ASN.2022050608

M3 - SCORING: Journal article

C2 - 35985817

VL - 33

SP - 1823

EP - 1831

JO - J AM SOC NEPHROL

JF - J AM SOC NEPHROL

SN - 1046-6673

IS - 10

ER -